Phenyl carbamate compounds for use in preventing or treating epilepsy

Abstract

A method for treatment or prevention epilepsy comprising administering a phenyl carbamate compound in a pharmaceutically effective amount to a subject in need of treatment or prevention of epilepsy is provided.

Claims

1. A method of treating epilepsy or an epilepsy-related symptom comprising administering a pharmaceutically effective amount of a compound represented by Chemical Formula 1 or a pharmaceutically acceptable salt thereof, to a subject in need of treating epilepsy, wherein the epilepsy is not pediatric epilepsy: ##STR00241## wherein the relative configuration at the carbon atoms bearing the asterisk (*) is (S); X is a chlorine, fluorine or iodine; n is 1 or 2; R.sup.1 is methyl group; A is a carbamoyl derivative represented by ##STR00242## B is hydrogen; and R.sup.2 is selected from the group consisting of hydrogen, a linear or branched alkyl group of C.sub.1-C.sub.4, a cycloalkyl group of C.sub.3-C.sub.8, and benzyl group.

2. A method of treating epilepsy or an epilepsy-related symptom, wherein the epilepsy is not pediatric epilepsy, comprising administering a pharmaceutically effective amount of a compound selected from the group consisting of: 1-(2-chlorophenyl)-(S)-1-hydroxypropyl-(S)-2-carbamate, 1-(2-chlorophenyl)-(S)-1-hydroxypropyl-(S)-2-N-methylcarbamate, 1-(2-chlorophenyl)-(S)-1-hydroxypropyl-(S)-2-N-propylcarbamate, 1-(2-chlorophenyl)-(S)-1-hydroxypropyl-(S)-2-N-isopropylcarbamate, 1-(2-chlorophenyl)-(S)-1-hydroxypropyl-(S)-2-N-cyclopropylcarbamate, 1-(2-chlorophenyl)-(S)-1-hydroxypropyl-(S)-2-N-cyclohexyl carbamate, 1-(2-fluorophenyl)-(S)-1-hydroxypropyl-(S)-2-carbamate, 1-(2-iodophenyl)-(S)-1-hydroxypropyl-(S)-2-carbamate, and combinations thereof; or a pharmaceutically acceptable salt thereof, to a subject in need of thereof.

3. The method according to claim 1, wherein the epilepsy-related symptom is an epileptic seizure.

4. The method according to claim 1, wherein the epileptic seizure is a partial seizure, a generalized seizure or an unclassified seizure.

Description

BRIEF DESCRIPTION OF DRAWINGS

(1) FIG. 1 is a graph showing ED50 values according to time measured through MES.

(2) FIG. 2 is a graph showing ED50 values according to time measured through scPTZ.

EXAMPLE

(3) The present invention is further explained in more detail with reference to the following examples. These examples, however, should not be interpreted as limiting the scope of the present invention in any manner.

Preparation Example 1

Synthesis of 1-(2-chlorophenyl)-trans-1-propene

(4) ##STR00012##

(5) 48 ml of 2-chlorobenzenaldehyde (0.42 mol) and 49.7 ml of 3-pentanone (0.47 mol) were dissolved in 600 mL of hexane in flask, and then stirred with raising the temperature. 53.6 ml of Boron trifluoride etherate (BF.sub.3OEt.sub.2, 0.42 mol) was added to the resultant under reflux conditions. When the reaction was completed, water was added thereto. After layer separation, the obtained organic layer was washed twice with 1M sodium hydroxide solution (1M NaOH), and then the separated organic layer was washed with water. The separated organic layer was dehydrated with anhydrous magnesium sulfate (MgSO.sub.4) and concentrated. The concentrated residue was purified by a silica gel column chromatography to produce the title compound (38 g, yield 58%).

(6) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.94 (d, J=4.8 Hz, 3H), 6.24 (m, 1H), 6.78 (d, J=14 Hz, 1H), 7.117.51 (m, 4H)

Preparation Example 2

Synthesis of 1-(2-chlorophenyl)-trans-1-butene

(7) ##STR00013##

(8) The substantially same method as described in Preparation Example 1 was conducted, except that 3-heptanone was used instead of 3-pentanone, to obtain the title compound (2.9 g, yield 83%).

(9) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.14 (d, J=7.6 Hz, 3H), 2.292.33 (m, 2H), 6.28 (dt, J=16 Hz, 6.4 Hz, 1H), 6.78 (d, J=15.6 Hz, 1H), 7.137.54 (m, 4H)

Preparation Example 3

Synthesis of 1-(2-chlorophenyl)-3-methyl-trans-1-butene

(10) ##STR00014##

(11) The substantially same method as described in Preparation Example 1 was conducted, except that 2,6-dimethyl-heptan-4-one was used instead of 3-pentanone, to obtain the title compound (8.0 g, yield 5090%).

(12) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.14 (d, J=6.8 Hz, 6H), 2.252.57 (m, 1H), 6.20 (dd, J=16 Hz, 7.2 Hz, 1H), 7.64 (d, J=16 Hz, 1H), 7.127.54 (m, 4H)

Preparation Example 4

Synthesis of 1-(2-chlorophenyl)-trans-1-hexene

(13) ##STR00015##

(14) The substantially same method as described in Preparation Example 1 was conducted, except that 6-undecanone was used instead of 3-pentanone, to obtain the title compound (10 g, yield 85%).

(15) .sup.1H NMR (400 MHz, CDCl.sub.3) 0.96 (1, J=7.2 Hz, 3H), 1.331.56 (m, 4H), 2.262.32 (m, 4H), 6.24 (dt, J=15.6 Hz, 7 Hz, 1H), 6.78 (d, J=16 Hz, 1H), 7.137.54 (m, 4H)

Preparation Example 5

Synthesis of 1-(2,4-dichlorophenyl)-trans-1-propene

(16) ##STR00016##

(17) The substantially same method as described in Preparation Example 1 was conducted, except that 2,4-dichlorobenzenaldehyde was used instead of 2-chlorobenzenaldehyde, to obtain the title compound (2.4 g, yield 57%).

(18) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.95 (dd, J=6.8 Hz, 1.6 Hz, 3H), 6.24 (m, 1H), 6.72 (d, J=15.6 Hz, 1H), 7.187.44 (m, 3H)

Preparation Example 6

Synthesis of 1-(2,4-dichlorophenyl)-trans-1-butene

(19) ##STR00017##

(20) The substantially same method as described in Preparation Example 5 was conducted, except that 3-heptanone was used instead of 3-pentanone, to obtain the title compound (2.1 g, yield 90%).

(21) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.14 (d, J=7.6 Hz, 3H), 2.202.33 (m, 2H), 6.26 (dt, J=16 Hz, 6.8 Hz, 1H), 6.70 (d, J=15.6 Hz, 1H), 7.187.46 (m, 3H)

Preparation Example 7

Synthesis of 1-(2,6-dichlorophenyl)-3-methyl-trans-1-butene

(22) ##STR00018##

(23) The substantially same method as described in Preparation Example 5 was conducted, except that 2,6-dimethyl-heptan-4-one was used instead of 3-pentanone, to obtain the title compound (0.23 g, yield 1040%).

(24) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.15 (d, J=6.8 Hz, 6H), 2.532.58 (m, 1H), 6.19 (dd, J=16.4 Hz, 6.8 Hz, 1H), 6.31 (d, J=16.4 Hz, 1H), 7.187.46 (m, 3H)

Preparation Example 8

Synthesis of 1-(2,4-dichlorophenyl)-trans-1-hexene

(25) ##STR00019##

(26) The substantially same method as described in Preparation Example 5 was conducted, except that 6-undecanone was used instead of 3-pentanone, to obtain the title compound (3.2 g, yield 4080%).

(27) .sup.1H NMR (400 MHz, CDCl.sub.3) 0.96 (t, J=7.2 Hz, 3H), 1.381.52 (m, 4H), 2.252.31 (m, 2H), 6.22 (dt, J=15.6 Hz, 6.8 Hz, 1H), 6.70 (d, J=15.6 Hz, 1H), 7.187.46 (m, 3H)

Preparation Example 9

Synthesis of 1-(2,6-dichlorophenyl)-trans-1-propene

(28) ##STR00020##

(29) The substantially same method as described in Preparation Example 1 was conducted, except that 2,6-dichlorobenzenaldehyde was used instead of 2-chlorobenzenaldehyde, to obtain the title compound (0.4 g, yield 1040%).

(30) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.98 (d, J=8 Hz, 3H), 6.236.31 (m, 1H), 6.40 (d, J=16 Hz, 1H), 7.057.32 (m, 3H)

Preparation Example 10

Synthesis of 1-(2,6-dichlorophenyl)-trans-1-butene

(31) ##STR00021##

(32) The substantially same method as described in Preparation Example 9 was conducted, except that 3-heptanone was used instead of 3-pentanone, to obtain the title compound (1.2 g, yield 1040%).

(33) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.17 (t, J=7.6 Hz, 3H), 2.302.37 (m, 2H), 6.29 (dt, J=16.4 Hz, 6 Hz, 1H), 6.37 (d, J=16.4 Hz, 1H), 7.057.32 (m, 3H)

Preparation Example 11

Synthesis of 1-(2,6-dichlorophenyl)-3-methyl-trans-1-butene

(34) ##STR00022##

(35) The substantially same method as described in Preparation Example 9 was conducted, except that 2,6-dimethyl-heptan-4-one was used instead of 3-pentanone, to obtain the title compound (0.23 g, yield 1040%).

(36) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.15 (d, J=6.8 Hz, 6H), 2.532.58 (m, 1H), 6.19 (dd, J=16.4 Hz, 6.8 Hz, 1H), 6.31 (d, J=16.4 Hz, 1H), 7.057.32 (m, 3H)

Preparation Example 12

Synthesis of 1-(2,6-dichlorophenyl)-trans-1-hexene

(37) ##STR00023##

(38) The substantially same method as described in Preparation Example 9 was conducted, except that 6-undecanone was used instead of 3-pentanone, to obtain the title compound (0.2 g, yield 1040%).

(39) .sup.1H NMR (400 MHz, CDCl.sub.3) 0.99 (t, J=7.2 Hz, 3H), 1.141.59 (m, 4H), 2.302.36 (m, 2H), 6.24 (dt, J=16 Hz, 6.6 Hz, 1H), 6.38 (d, J=16.4 Hz, 1H), 7.057.33 (m, 3H)

Preparation Example 13

Synthesis of 1-(2,3-dichlorophenyl)-trans-1-propene

(40) ##STR00024##

(41) The substantially same method as described in Preparation Example 1 was conducted, except that 2,3-dichlorobenzenaldehyde was used instead of 2-chlorobenzenaldehyde, to obtain the title compound (0.2 g, yield 1040%).

(42) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.94 (d, J=4.8 Hz, 3H), 6.24 (m, 1H), 6.78 (d, J=14 Hz, 1H), 7.117.51 (m, 3H)

Preparation Example 14

Synthesis of 1-(2-chlorophenyl)-(S,S)-1,2-propanediol

(43) ##STR00025##

(44) 1-(2-chlorophenyl)-trans-1-propene (1.5 g, Preparation Example 1) was dissolved in 30 mL of the mixture of t-BuOH/H.sub.2O (1:1 (V/V)). At 0 C., AD-mix- (Aldrich, U.S.A.) (13.7 g) and methane sulfone amide (CH.sub.3SO.sub.2NH.sub.2, 0.76 g, 0.0080 mol) were added thereto and stirred for overnight. When the reaction was completed, the obtained product was washed with an aqueous solution of sodium sulfite (Na.sub.2SO.sub.3) and ethylacetate (EA). Then, the organic layer was dehydrated with anhydrous magnesium sulfate (MgSO.sub.4), filtrated, and concented under reduced pressure. The concentrated residue was purified by a silica gel column chromatography to produce the title compound (1.65 g, yield 90%).

(45) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.20 (d, J=6.4 Hz, 3H), 2.48 (d, J=4.0 Hz 1H), 2.92 (d, J=4.4 Hz, 1H), 3.933.97 (m, 1H), 4.97 (t, J=4.8 Hz, 1H), 7.227.51 (m, 4H)

(46) .sup.13CNMR (100 MHz, CDCl.sub.3) 18.8, 71.5, 74.4, 127.1, 128.1, 128.9, 129.5, 132.6, 138.9

Preparation Example 15

Synthesis of 1-(2-chlorophenyl)-(R,R)-1,2-propanediol

(47) ##STR00026##

(48) 1-(2-chlorophenyl)-trans-1-propene (2.5 g, Preparation Example 1) was dissolved in 50 mL of the mixture of t-BuOH/H.sub.2O (1:1 (V/V)). At 0 C., AD-mix- (Aldrich, U.S.A.) (23.5 g) and methane sulfone amide (CH.sub.3SO.sub.2NH.sub.2, 1.27 g, 0.013 mol) were added thereto and stirred for overnight. When the reaction was completed, the obtained product was washed with an aqueous solution of sodium sulfite (Na.sub.2SO.sub.3) and ethylacetate (EA). Then, the organic layer was dehydrated with anhydrous magnesium sulfate (MgSO.sub.4), filtrated, and concented under reduced pressure. The concentrated residue was purified by a silica gel column chromatography to produce the title compound (2.96 g, yield 90%).

(49) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.20 (d, J=6.4 Hz, 3H), 2.48 (d, J=4.0 Hz, 1H), 2.92 (d, J=4.4 Hz, 1H), 3.933.97 (m, 1H), 4.97 (t, J=4.8 Hz, 1H), 7.227.51 (m, 4H)

Preparation Example 16

Synthesis of the mixture of 1-(2-chlorophenyl)-(S,S)-1,2-propanediol and 1-(2-chlorophenyl)-(R,R)-1,2-propanediol

(50) ##STR00027##

(51) 1-(2-chlorophenyl)-trans-1-propene (6.53 g, Preparation Example 1) was dissolved in 45 mL of the mixture of acetone/t-BuOH/H.sub.2O (5:1:1 V/V). At the room temperature, N-methylmorpholine-N-oxide (7.51 g) and OsO.sub.4 (0.54 g) were added thereto and stirred for 2-3 hours. When the reaction was completed, the obtained product was washed with water and methylenechloride (MC). Then, the organic layer was dehydrated with anhydrous magnesium sulfate (MgSO.sub.4), filtrated, and concented under reduced pressure. The concentrated residue was purified by a silica gel column chromatography to produce the title compound (6.42 g, yield 80%).

(52) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.20 (d, J=6.4 Hz, 3H), 2.48 (d, J=4.0 Hz, 1H), 2.92 (d, J=4.4 Hz, 1H), 3.933.97 (m, 1H), 4.97 (t, J=4.8 Hz, 1H), 7.227.51 (m, 4H)

Preparation Example 17

Synthesis of 1-(2-chlorophenyl)-(S,S)-1,2-butanediol

(53) ##STR00028##

(54) The substantially same method as described in Preparation Example 14 was conducted, except that 1-(2-chlorophenyl)-trans-1-butene (Preparation Example 2) was used instead of 1-(2-chlorophenyl)-trans-1-propene (Preparation Example 1), to obtain the title compound (0.36 g, yield 95%).

(55) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.01 (1, J=7.4 Hz, 3H), 1.521.65 (m, 2H), 2.01 (d, J=4.4 Hz, 1H), 2.74 (d, J=5.2 Hz, 1H), 3.693.75 (m, 1H), 5.05 (t, J=5.0 Hz, 1H), 7.237.54 (m, 4H)

Preparation Example 18

Synthesis of 1-(2-chlorophenyl)-(R,R)-1,2-butanediol

(56) ##STR00029##

(57) The substantially same method as described in Preparation Example 15 was conducted, except that 1-(2-chlorophenyl)-trans-1-butene (Preparation Example 2) was used instead of 1-(2-chlorophenyl)-trans-1-propene (Preparation Example 1), to obtain the title compound (0.84 g, yield 6095%).

(58) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.01 (1, J=7.4 Hz, 3H), 1.521.65 (m, 2H), 2.01 (d, J=4.4 Hz, 1H), 2.74 (d, J=5.2 Hz, 1H), 3.693.75 (m, 1H), 5.05 (t, J=5.0 Hz, 1H), 7.237.54 (m, 4H)

Preparation Example 19

Synthesis of the mixture of 1-(2-chlorophenyl)-(S,S)-1,2-butanediol and 1-(2-chlorophenyl)-(R,R)-1,2-butanediol

(59) ##STR00030##

(60) The substantially same method as described in Preparation Example 16 was conducted, except that 1-(2-chlorophenyl)-trans-1-butene (Preparation Example 2) was used instead of 1-(2-chlorophenyl)-trans-1-propene (Preparation Example 1), to obtain the title compound (5.1 g, yield 6090%).

(61) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.01 (1, J=7.4 Hz, 3H), 1.521.65 (m, 2H), 2.01 (d, J=4.4 Hz, 1H), 2.74 (d, J=5.2 Hz, 1H), 3.693.75 (m, 1H), 5.05 (t, J=5.0 Hz, 1H), 7.237.54 (m, 4H)

Preparation Example 20

Synthesis of 1-(2-chlorophenyl)-3-methyl-(S,S)-1,2-butanediol

(62) ##STR00031##

(63) The substantially same method as described in Preparation Example 14 was conducted, except that 1-(2-chlorophenyl)-3-methyl-trans-1-butene (Preparation Example 3) was used instead of 1-(2-chlorophenyl)-trans-1-propene (Preparation Example 1), to obtain the title compound (0.96 g, yield 6090%).

(64) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.07 (1, J=7.2 Hz, 6H), 1.831.89 (m, 1H), 1.92 (d, J=5.6 Hz, 1H), 2.69 (d, J=6.4 Hz, 1H), 3.533.56 (m, 1H), 5.225.25 (m, 1H), 7.237.55 (m, 4H)

Preparation Example 21

Synthesis of 1-(2-chlorophenyl)-3-methyl-(R,R)-1,2-butanediol

(65) ##STR00032##

(66) The substantially same method as described in Preparation Example 15 was conducted, except that 1-(2-chlorophenyl)-3-methyl-trans-1-butene (Preparation Example 3) was used instead of 1-(2-chlorophenyl)-trans-1-propene (Preparation Example 1), to obtain the title compound (4.2 g, yield 6090%).

(67) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.07 (1, J=7.2 Hz, 6H), 1.821.90 (m, 1H), 1.93 (d, J=5.6 Hz, 1H), 2.79 (d, J=6 Hz, 1H), 3.533.57 (m, 1H), 5.235.25 (m, 1H), 7.237.54 (m, 4H)

Preparation Example 22

Synthesis of the mixture of 1-(2-chlorophenyl)-3-methyl-(S,S)-1,2-butanediol and 1-(2-chlorophenyl)-3-methyl-(R,R)-1,2-butanediol

(68) ##STR00033##

(69) The substantially same method as described in Preparation Example 16 was conducted, except that 1-(2-chlorophenyl)-3-methyl-trans-1-butene (Preparation Example 3) was used instead of 1-(2-chlorophenyl)-trans-1-propene (Preparation Example 1), to obtain the title compound (0.8 g, yield 6090%).

(70) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.07 (1, J=7.2 Hz, 6H), 1.831.90 (m, 1H), 1.92 (d, J=5.6 Hz, 1H), 2.69 (d, J=6.4 Hz, 1H), 3.533.56 (m, 1H), 5.225.25 (m, 1H), 7.237.55 (m, 4H)

Preparation Example 23

Synthesis of 1-(2-chlorophenyl)-(S,S)-1,2-hexanediol

(71) ##STR00034##

(72) The substantially same method as described in Preparation Example 14 was conducted, except that 1-(2-chlorophenyl)-trans-1-hexene (Preparation Example 4) was used instead of 1-(2-chlorophenyl)-trans-1-propene (Preparation Example 1), to obtain the title compound (0.37 g, yield 90%).

(73) .sup.1H NMR (400 MHz, CDCl.sub.3) 0.90 (t, J=7.2 Hz, 3H), 1.351.65 (m, 6H), 2.08 (d, J=4.4 Hz, 1H), 2.71 (d, J=5.2 Hz, 1H), 3.783.83 (m, 1H), 5.04 (t, J=5.0 Hz, 1H), 7.237.53 (m, 4H)

Preparation Example 24

Synthesis of 1-(2-chlorophenyl)-(R,R)-1,2-hexanediol

(74) ##STR00035##

(75) The substantially same method as described in Preparation Example 15 was conducted, except that 1-(2-chlorophenyl)-trans-1-hexene (Preparation Example 4) was used instead of 1-(2-chlorophenyl)-trans-1-propene (Preparation Example 1), to obtain the title compound (4.2 g, yield 6090%).

(76) .sup.1H NMR (400 MHz, CDCl.sub.3) 0.91 (1, J=6.6 Hz, 3H), 1.351.65 (m, 6H), 2.08 (d, J=4.8 Hz, 1H), 2.70 (d, J=5.2 Hz, 1H), 3.803.83 (m, 1H), 5.05 (t, J=5.0 Hz, 1H), 7.247.56 (m, 4H)

Preparation Example 25

Synthesis of the mixture of 1-(2-chlorophenyl)-(S,S)-1,2-hexanediol and 1-(2-chlorophenyl)-(R,R)-1,2-hexanediol

(77) ##STR00036##

(78) The substantially same method as described in Preparation Example 16 was conducted, except that 1-(2-chlorophenyl)-trans-1-hexene (Preparation Example 4) was used instead of 1-(2-chlorophenyl)-trans-1-propene (Preparation Example 1), to obtain the title compound (7.9 g, yield 6090%).

(79) .sup.1H NMR (400 MHz, CDCl.sub.3) 0.90 (t, J=7.2 Hz, 3H), 1.261.55 (m, 6H), 2.08 (d, J=4.4 Hz, 1H), 2.71 (d, J=5.6 Hz, 1H), 3.783.84 (m, 1H), 5.04 (t, J=3.2 Hz, 1H), 7.247.55 (m, 4H)

Preparation Example 26

Synthesis of 1-(2,4-dichlorophenyl)-(S,S)-1,2-propanediol

(80) ##STR00037##

(81) The substantially same method as described in Preparation Example 14 was conducted, except that 1-(2,4-dichlorophenyl)-trans-1-propene (Preparation Example 5) was used instead of 1-(2-chlorophenyl)-trans-1-propene (Preparation Example 1), to obtain the title compound (0.33 g, yield 6095%).

(82) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.22 (d, J=6.4 Hz, 3H), 2.10 (d, J=4.4 Hz, 1H), 2.71 (d, J=4.8 Hz, 1H), 3.903.95 (m, 1H), 4.94 (t, J=5.0 Hz, 1H), 7.31 (dd, J=2.0 Hz, J=8.0 Hz, 1H), 7.40 (d, J=2.0 Hz, 1H), 7.49 (d, J=8.4 Hz, 1H)

Preparation Example 27

Synthesis of 1-(2,4-dichlorophenyl)-(R,R)-1,2-propanediol

(83) ##STR00038##

(84) The substantially same method as described in Preparation Example 15 was conducted, except that 1-(2,4-dichlorophenyl)-trans-1-propene (Preparation Example 5) was used instead of 1-(2-chlorophenyl)-trans-1-propene (Preparation Example 1), to obtain the title compound (0.45 g, yield 6095%).

(85) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.22 (d, J=6.4 Hz, 3H), 2.10 (d, J=4.4 Hz, 1H), 2.71 (d, J=4.8 Hz, 1H), 3.903.95 (m, 1H), 4.94 (t, J=5.0 Hz, 1H), 7.317.49 (m, 3H)

Preparation Example 28

Synthesis of the mixture of 1-(2,4-dichlorophenyl)-(S,S)-1,2-propanediol and 1-(2,4-dichlorophenyl)-(R,R)-1,2-propanediol

(86) ##STR00039##

(87) The substantially same method as described in Preparation Example 16 was conducted, except that 1-(2,4-dichlorophenyl)-trans-1-propene (Preparation Example 5) was used instead of 1-(2-chlorophenyl)-trans-1-propene (Preparation Example 1), to obtain the title compound (0.45 g, yield 6095%).

(88) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.22 (d, J=6.4 Hz, 3H), 2.10 (d, J=4.4 Hz, 1H), 2.71 (d, J=4.8 Hz, 1H), 3.903.95 (m, 1H), 4.94 (t, J=5.0 Hz, 1H), 7.317.49 (m, 3H)

Preparation Example 29

Synthesis of 1-(2,4-dichlorophenyl)-(S,S)-1,2-butanediol

(89) ##STR00040##

(90) The substantially same method as described in Preparation Example 14 was conducted, except that 1-(2,4-dichlorophenyl)-trans-1-butene (Preparation Example 6) was used instead of 1-(2-chlorophenyl)-trans-1-propene (Preparation Example 1), to obtain the title compound (0.32 g, yield 90%).

(91) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.02 (1, J=7.4 Hz, 3H), 1.541.61 (m, 2H), 2.07 (d, J=4.8 Hz, 1H), 2.74 (d, J=4.8 Hz, 1H), 3.653.68 (m, 1H), 5.01 (t, J=5.0 Hz, 1H), 7.317.49 (m, 3H)

Preparation Example 30

Synthesis of 1-(2,4-dichlorophenyl)-(R,R)-1,2-butanediol

(92) ##STR00041##

(93) The substantially same method as described in Preparation Example 15 was conducted, except that 1-(2,4-dichlorophenyl)-trans-1-butene (Preparation Example 6) was used instead of 1-(2-chlorophenyl)-trans-1-propene (Preparation Example 1), to obtain the title compound (0.43 g, yield 6090%).

(94) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.02 (1, J=7.4 Hz, 3H), 1.541.61 (m, 2H), 2.07 (d, J=4.8 Hz, 1H), 2.74 (d, J=4.8 Hz, 1H), 3.653.68 (m, 1H), 5.01 (t, J=5.0 Hz, 1H), 7.317.49 (m, 3H)

Preparation Example 31

Synthesis of the mixture of 1-(2,4-dichlorophenyl)-(S,S)-1,2-butanediol and 1-(2,4-dichlorophenyl)-(R,R)-1,2-butanediol

(95) ##STR00042##

(96) The substantially same method as described in Preparation Example 16 was conducted, except that 1-(2,4-dichlorophenyl)-trans-1-butene (Preparation Example 6) was used instead of 1-(2-chlorophenyl)-trans-1-propene (Preparation Example 1), to obtain the title compound (0.33 g, yield 6090%).

(97) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.02 (1, J=7.4 Hz, 3H), 1.541.61 (m, 2H), 2.07 (d, J=4.8 Hz, 1H), 2.74 (d, J=4.8 Hz, 1H), 3.653.68 (m, 1H), 5.01 (t, J=5.0 Hz, 1H), 77.317.49 (m, 3H)

Preparation Example 32

Synthesis of 1-(2,4-dichlorophenyl)-3-methyl-(S,S)-1,2-butanediol

(98) ##STR00043##

(99) The substantially same method as described in Preparation Example 14 was conducted, except that 1-(2,4-dichlorophenyl)-3-methyl-trans-1-butene (Preparation Example 7) was used instead of 1-(2-chlorophenyl)-trans-1-propene (Preparation Example 1), to obtain the title compound (0.25 g, yield 6095%).

(100) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.00 (d, J=6.8 Hz, 6H), 1.601.65 (m, 1H), 2.35 (d, J=4.0 Hz, 1H), 3.12 (d, J=8.4 Hz, 1H), 4.134.18 (m, 1H), 5.36 (t, J=7.6 Hz, 1H), 7.177.35 (m, 3H)

Preparation Example 33

Synthesis of 1-(2,4-dichlorophenyl)-3-methyl-(R,R)-1,2-butanediol

(101) ##STR00044##

(102) The substantially same method as described in Preparation Example 15 was conducted, except that 1-(2,4-dichlorophenyl)-3-methyl-trans-1-butene (Preparation Example 7) was used instead of 1-(2-chlorophenyl)-trans-1-propene (Preparation Example 1), to obtain the title compound (0.36 g, yield 6095%).

(103) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.00 (d, J=6.8 Hz, 6H), 1.601.65 (m, 1H), 2.35 (d, J=4.0 Hz, 1H), 3.12 (d, J=8.4 Hz, 1H), 4.134.18 (m, 1H), 5.36 (t, J=7.6 Hz, 1H), 7.177.35 (m, 3H)

Preparation Example 34

Synthesis of the mixture of 1-(2,4-dichlorophenyl)-3-methyl-(S,S)-1,2-butanediol and 1-(2,4-dichlorophenyl)-3-methyl-(R,R)-1,2-butanediol

(104) ##STR00045##

(105) The substantially same method as described in Preparation Example 16 was conducted, except that 1-(2,4-dichlorophenyl)-3-methyl-trans-1-butene (Preparation Example 7) was used instead of 1-(2-chlorophenyl)-trans-1-propene (Preparation Example 1), to obtain the title compound (0.26 g, yield 6095%).

(106) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.00 (d, J=6.8 Hz, 6H), 1.601.65 (m, 1H), 2.35 (d, J=4.0 Hz, 1H), 3.12 (d, J=8.4 Hz, 1H), 4.134.18 (m, 1H), 5.36 (t, J=7.6 Hz, 1H), 7.177.35 (m, 3H)

Preparation Example 35

Synthesis of 1-(2,4-dichlorophenyl)-(S,S)-1,2-hexanediol

(107) ##STR00046##

(108) The substantially same method as described in Preparation Example 14 was conducted, except that 1-(2,4-dichlorophenyl)-trans-1-hexene (Preparation Example 8) was used instead of 1-(2-chlorophenyl)-trans-1-propene (Preparation Example 1), to obtain the title compound (1.1 g, yield 6090%).

(109) .sup.1H NMR (400 MHz, CDCl.sub.3) 0.890.93 (m, 3H), 1.301.39 (m, 2H), 1.491.52 (m, 2H), 1.561.62 (m, 2H), 2.05 (d, J=5.2 Hz, 1H), 2.74 (d, J=5.2 Hz, 1H), 3.723.77 (m, 1H), 4.98 (t, J=4.8 Hz, 1H), 7.287.50 (m, 3H)

Preparation Example 36

Synthesis of 1-(2,4-dichlorophenyl)-(R,R)-1,2-hexanediol

(110) ##STR00047##

(111) The substantially same method as described in Preparation Example 15 was conducted, except that 1-(2,4-dichlorophenyl)-trans-1-hexene (Preparation Example 8) was used instead of 1-(2-chlorophenyl)-trans-1-propene (Preparation Example 1), to obtain the title compound (1.2 g, yield 6095%).

(112) .sup.1H NMR (400 MHz, CDCl.sub.3) 0.890.93 (m, 3H), 1.301.39 (m, 2H), 1.491.52 (m, 2H), 1.561.62 (m, 2H), 2.05 (d, J=5.2 Hz, 1H), 2.74 (d, J=5.2 Hz, 1H), 3.723.77 (m, 1H), 4.98 (t, J=4.8 Hz, 1H), 7.287.50 (m, 3H)

Preparation Example 37

Synthesis of the mixture of 1-(2,4-dichlorophenyl)-(S,S)-1,2-hexanediol and 1-(2,4-dichlorophenyl)-(R,R)-1,2-hexanediol

(113) ##STR00048##

(114) The substantially same method as described in Preparation Example 16 was conducted, except that 1-(2,4-dichlorophenyl)-trans-1-hexene (Preparation Example 8) was used instead of 1-(2-chlorophenyl)-trans-1-propene (Preparation Example 1), to obtain the title compound (0.67 g, yield 6095%).

(115) .sup.1H NMR (400 MHz, CDCl.sub.3) 0.890.93 (m, 3H), 1.301.39 (m, 2H), 1.491.52 (m, 2H), 1.561.62 (m, 2H), 2.05 (d, J=5.2 Hz, 1H), 2.74 (d, J=5.2 Hz, 1H), 3.723.77 (m, 1H), 4.98 (t, J=4.8 Hz, 1H), 7.287.50 (m, 3H)

Preparation Example 38

Synthesis of 1-(2,6-dichlorophenyl)-(S,S)-1,2-propanediol

(116) ##STR00049##

(117) The substantially same method as described in Preparation Example 14 was conducted, except that 1-(2,6-dichlorophenyl)-trans-1-propene (Preparation Example 9) was used instead of 1-(2-chlorophenyl)-trans-1-propene (Preparation Example 1), to obtain the title compound (0.9 g, yield 6090%).

(118) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.10 (d, J=6.4 Hz, 3H), 2.72 (d, J=2.4 Hz, 1H), 3.10 (d, J=8.4 Hz, 1H), 4.474.54 (m, 1H), 5.24 (t, J=8.8 Hz, 1H), 7.187.36 (m, 3H)

Preparation Example 39

Synthesis of 1-(2,6-dichlorophenyl)-(R,R)-1,2-propanediol

(119) ##STR00050##

(120) The substantially same method as described in Preparation Example 15 was conducted, except that 1-(2,6-dichlorophenyl)-trans-1-propene (Preparation Example 9) was used instead of 1-(2-chlorophenyl)-trans-1-propene (Preparation Example 1), to obtain the title compound (0.84 g, yield 6090%).

(121) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.10 (d, J=6.4 Hz, 3H), 2.72 (d, J=2.4 Hz, 1H), 3.10 (d, J=8.4 Hz, 1H), 4.474.54 (m, 1H), 5.24 (t, J=8.8 Hz, 1H), 7.187.36 (m, 3H)

Preparation Example 40

Synthesis of the mixture of 1-(2,6-dichlorophenyl)-(S,S)-1,2-propanediol and 1-(2,6-dichlorophenyl)-(R,R)-1,2-propanediol

(122) ##STR00051##

(123) The substantially same method as described in Preparation Example 16 was conducted, except that 1-(2,6-dichlorophenyl)-trans-1-propene (Preparation Example 9) was used instead of 1-(2-chlorophenyl)-trans-1-propene (Preparation Example 1), to obtain the title compound (0.91 g, yield 6090%).

(124) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.10 (d, J=6.4 Hz, 3H), 2.72 (d, J=2.4 Hz, 1H), 3.10 (d, J=8.4 Hz, 1H), 4.474.54 (m, 1H), 5.24 (t, J=8.8 Hz, 1H), 7.187.36 (m, 3H)

Preparation Example 41

Synthesis of 1-(2,6-dichlorophenyl)-(S,S)-1,2-butanediol

(125) ##STR00052##

(126) The substantially same method as described in Preparation Example 14 was conducted, except that 1-(2,6-dichlorophenyl)-trans-1-butene (Preparation Example 10) was used instead of 1-(2-chlorophenyl)-trans-1-propene (Preparation Example 1), to obtain the title compound (1.23 g, yield 6095%).

(127) .sup.1H NMR (400 MHz, CDCl.sub.3) 0.97 (t, J=7.6 Hz, 3H), 1.261.53 (m, 2H), 2.64 (dd, J=0.8 Hz, J=4.0 Hz, 1H), 3.14 (d, J=8.4 Hz, 1H), 4.224.26 (m, 1H), 5.26 (t, J=8.4 Hz, 1H), 7.177.35 (m, 3H)

Preparation Example 42

Synthesis of 1-(2,6-dichlorophenyl)-(R,R)-1,2-butanediol

(128) ##STR00053##

(129) The substantially same method as described in Preparation Example 15 was conducted, except that 1-(2,6-dichlorophenyl)-trans-1-butene (Preparation Example 10) was used instead of 1-(2-chlorophenyl)-trans-1-propene (Preparation Example 1), to obtain the title compound (0.96 g, yield 6095%).

(130) .sup.1H NMR (400 MHz, CDCl.sub.3) 0.97 (t, J=7.6 Hz, 3H), 1.261.53 (m, 2H), 2.64 (dd, J=0.8 Hz, J=4.0 Hz, 1H), 3.14 (d, J=8.4 Hz, 1H), 4.224.26 (m, 1H), 5.26 (t, J=8.4 Hz, 1H), 7.177.35 (m, 3H)

Preparation Example 43

Synthesis of the mixture of 1-(2,6-dichlorophenyl)-(S,S)-1,2-butanediol and 1-(2,6-dichlorophenyl)-(R,R)-1,2-butanediol

(131) ##STR00054##

(132) The substantially same method as described in Preparation Example 16 was conducted, except that 1-(2,6-dichlorophenyl)-trans-1-butene (Preparation Example 10) was used instead of 1-(2-chlorophenyl)-trans-1-propene (Preparation Example 1), to obtain the title compound (0.86 g, yield 6095%).

(133) .sup.1H NMR (400 MHz, CDCl.sub.3) 0.97 (t, J=7.6 Hz, 3H), 1.261.53 (m, 2H), 2.64 (dd, J=0.8 Hz, J=4.0 Hz, 1H), 3.14 (d, J=8.4 Hz, 1H), 4.224.26 (m, 1H), 5.26 (t, J=8.4 Hz, 1H), 7.177.35 (m, 3H)

Preparation Example 44

Synthesis of 1-(2,6-dichlorophenyl)-3-methyl-(S,S)-1,2-butanediol

(134) ##STR00055##

(135) The substantially same method as described in Preparation Example 14 was conducted, except that 1-(2,6-dichlorophenyl)-3-methyl-trans-1-butene (Preparation Example 11) was used instead of 1-(2-chlorophenyl)-trans-1-propene (Preparation Example 1), to obtain the title compound (0.25 g, yield 6095%).

(136) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.00 (d, J=6.8 Hz, 6H), 1.601.65 (m, 1H), 2.35 (d, J=4.0 Hz, 1H), 3.12 (d, J=8.4 Hz, 1H), 4.134.18 (m, 1H), 5.36 (t, J=7.6 Hz, 1H), 7.177.35 (m, 3H)

Preparation Example 45

Synthesis of 1-(2,6-dichlorophenyl)-3-methyl-(R,R)-1,2-butanediol

(137) ##STR00056##

(138) The substantially same method as described in Preparation Example 15 was conducted, except that 1-(2,6-dichlorophenyl)-3-methyl-trans-1-butene (Preparation Example 11) was used instead of 1-(2-chlorophenyl)-trans-1-propene (Preparation Example 1), to obtain the title compound (0.37 g, yield 6095%).

(139) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.00 (d, J=6.8 Hz, 6H), 1.601.65 (m, 1H), 2.35 (d, J=4.0 Hz, 1H), 3.12 (d, J=8.4 Hz, 1H), 4.134.18 (m, 1H), 5.36 (t, J=7.6 Hz, 1H), 7.177.35 (m, 3H)

Preparation Example 46

Synthesis of the mixture of 1-(2,6-dichlorophenyl)-3-methyl-(S,S)-1,2-butanediol and 1-(2,6-dichlorophenyl)-3-methyl-(R,R)-1,2-butanediol

(140) ##STR00057##

(141) The substantially same method as described in Preparation Example 16 was conducted, except that 1-(2,6-dichlorophenyl)-3-methyl-trans-1-butene (Preparation Example 11) was used instead of 1-(2-chlorophenyl)-trans-1-propene (Preparation Example 1), to obtain the title compound (0.47 g, yield 6095%).

(142) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.00 (d, J=6.8 Hz, 6H), 1.601.65 (m, 1H), 2.35 (d, J=4.0 Hz, 1H), 3.12 (d, J=8.4 Hz, 1H), 4.134.18 (m, 1H), 5.36 (t, J=7.6 Hz, 1H), 7.177.35 (m, 3H)

Preparation Example 47

Synthesis of 1-(2,6-dichlorophenyl)-(S,S)-1,2-hexanediol

(143) ##STR00058##

(144) The substantially same method as described in Preparation Example 14 was conducted, except that 1-(2,6-dichlorophenyl)-trans-1-hexene (Preparation Example 12) was used instead of 1-(2-chlorophenyl)-trans-1-propene (Preparation Example 1), to obtain the title compound (0.36 g, yield 6090%).

(145) .sup.1H NMR (400 MHz, CDCl.sub.3) 0.85 (t, J=6.8 Hz, 3H), 1.201.31 (m, 4H), 1.451.53 (m, 2H), 2.612.62 (m, 1H), 3.12 (d, J=8.4 Hz, 1H), 4.284.33 (m, 1H), 5.25 (t, J=8.4 Hz, 1H), 7.187.35 (m, 3H)

Preparation Example 48

Synthesis of 1-(2,6-dichlorophenyl)-(R,R)-1,2-hexanediol

(146) ##STR00059##

(147) The substantially same method as described in Preparation Example 15 was conducted, except that 1-(2,6-dichlorophenyl)-trans-1-hexene (Preparation Example 12) was used instead of 1-(2-chlorophenyl)-trans-1-propene (Preparation Example 1), to obtain the title compound (0.58 g, yield 6090%).

(148) .sup.1H NMR (400 MHz, CDCl.sub.3) 0.85 (t, J=6.8 Hz, 3H), 1.201.31 (m, 4H), 1.451.53 (m, 2H), 2.612.62 (m, 1H), 3.12 (d, J=8.4 Hz, 1H), 4.284.33 (m, 1H), 5.25 (t, J=8.4 Hz, 1H), 7.187.35 (m, 3H)

Preparation Example 49

Synthesis of the mixture of 1-(2,6-dichlorophenyl)-(S,S)-1,2-hexanediol and 1-(2,6-dichlorophenyl)-(R,R)-1,2-hexanediol

(149) ##STR00060##

(150) The substantially same method as described in Preparation Example 16 was conducted, except that 1-(2,6-dichlorophenyl)-trans-1-hexene (Preparation Example 12) was used instead of 1-(2-chlorophenyl)-trans-1-propene (Preparation Example 1), to obtain the title compound (0.62 g, yield 6090%).

(151) .sup.1H NMR (400 MHz, CDCl.sub.3) 0.85 (t, J=6.8 Hz, 3H), 1.201.31 (m, 4H), 1.451.53 (m, 2H), 2.612.62 (m, 1H), 3.12 (d, J=8.4 Hz, 1H), 4.284.33 (m, 1H), 5.25 (t, J=8.4 Hz, 1H), 7.187.35 (m, 3H)

Preparation Example 50

Synthesis of methyl 2-(2-chlorophenyl)-(R)-2-hydroxyacetate

(152) ##STR00061##

(153) 15 g of (R)-2-chloromandelic acid was mixed with methanol (CH.sub.3OH, 150 ml) and phosphorus chloride oxide (POCl.sub.3, 0.76 ml) in a flask by stirring using a magnetic stirrer at the room temperature for 6 hours. When the reaction was completed, the obtained product was washed with an aqueous solution of sodium sulfite (Na.sub.2SO.sub.3) and ethylacetate (EA). Then, the organic layer was dehydrated with anhydrous magnesium sulfate (MgSO.sub.4), filtrated, and concented under reduced pressure. The concentrated residue was purified by a silica gel column chromatography to produce the title compound (15.64 g, yield 95%).

(154) .sup.1H NMR (400 MHz, CDCl.sub.3) 3.59 (d, J=5.2, 1H), 3.79 (t, J=6.0, 3H), 5.59 (d, J=5.2, 1H), 7.287.43 (m, 4H)

Preparation Example 51

Synthesis of 2-(2-chlorophenyl)-(R)-2-hydroxy-N-methoxy-N-methylacetamide

(155) ##STR00062##

(156) N,O-dimethylhydroxylamine hydrochloride (N,O-dimethylhydroxylamine.HCl, 15.2 g) was dissolved in dichloromethane (DCM, 150 ml), and cooled to 0 C. using an ice-bath. Then, 77.7 ml of 2.0M trimethylaluminium in hexane was slowly added thereto in drop-wise manner for 30 minutes. Thereafter, the ice-bath was removed, and the obtained product was stirred at the room temperature for 2 hours. Methyl-2-(2-chlorophenyl)-(R)-2-hydroxyacetate (15.64 g) dissolved in dichloromethane (DCM, 150 ml) was added in drop-wise manner thereto at the room temperature for 30 minutes, and subjected to reflux for 12 hours. When the reaction was completed, the obtained product was cooled to 0 C., and washed by a slow drop-wise addition of hydrochloric acid (HCl, 200 ml). The obtained organic layer was washed with distilled water and brine, dehydrated with anhydrous magnesium sulfate (MgSO.sub.4), filtrated, and concented under reduced pressure. The concentrated residue was purified by a silica gel column chromatography to produce the title compound (14.68 g, yield 82%).

(157) .sup.1H NMR (400 MHz, CDCl.sub.3) 3.23 (s, 3H), 3.28 (s, 3H), 4.33 (d, J=6.0 Hz, 1H), 5.81 (d, J=5.6 Hz, 1H), 7.237.42 (m, 4H)

Preparation Example 52

Synthesis of 2-(2-chlorophenyl)-N-methoxy-(R)-2-(t-butyl dimethlysiloxy)-N-methylacetamide

(158) ##STR00063##

(159) 2-(2-chlorophenyl)-(R)-2-hydroxy-N-methoxy-N-methylacetamide (0.81 g, 3.52 mmol) obtained in Preparation Example 51 was dissolved in dichloromethane (DCM), and cooled to 0 C. Imedazole (0.36 g, 5.28 mmol) was slowly added, and stirred. TBDMS-Cl (t-butyldimethylsily chloride, 0.79 g, 5.28 mmol) was slowly added. When the reaction was completed, the reaction mixture was quenched with H.sub.2O. The organic layer was separated and collected. The aqueous layer was extracted with CH.sub.2Cl.sub.2 (300 mL), dried over MgSO.sub.4. Concentration under vacuum provided a title compound. (0.97 g, 8095%).

(160) .sup.1H NMR (400 MHz, CDCl.sub.3) 0.03 (s, 3H), 0.14 (s, 3H), 0.94 (s, 9H), 2.97 (s, 3H), 3.02 (s, 3H), 5.83 (s, 1H), 7.257.60 (m, 4H)

Preparation Example 53

Synthesis of 1-(2-chlorophenyl)-(R)-1-(t-butyldimethyl-siloxy)propane-2-on

(161) ##STR00064##

(162) 2-(2-chlorophenyl)-N-methoxy-(R)-2-(t-butyldimethylsiloxy)-N-methylacetamide (0.9 g) obtained in Preparation Example 52 was dissolved in tetrahydrofuran (THF), and cooled to 0 C. 3.0M methyl magnesium bromide (MeMgBr, 2.18 ml) solution in ether was added thereto in drop-wise manner for 30 minutes, and the obtained product was stirred at 0 C. When the reaction was completed, diethylether was added thereto. The obtained product was washed with 10% (w/v) potassium hydrogen sulfate (KHSO.sub.4, 100 ml) and then, washed again with brine. The obtained organic layer was dehydrated with anhydrous magnesium sulfate (MgSO.sub.4), filtrated, and concentrated under reduced pressure. The concentrated residue was purified by a silica gel column chromatography to produce the title compound (0.69 g, yield 8595%).

(163) .sup.1H NMR (400 MHz, CDCl.sub.3) 0.3 (s, 3H), 0.14 (s, 3H), 0.94 (s, 9H), 2.18 (s, 3H), 5.50 (s, 1H), 7.277.56 (m, 4H)

Preparation Example 54

Synthesis of 1-(2-chlorophenyl)-(R)-1-(t-butyldimethyl-siloxy)-(S)-2-propanol

(164) ##STR00065##

(165) 1-(2-chlorophenyl)-(R)-1-(t-butyldimethyl-siloxy)propane-2-on (0.14 g) obtained in Preparation Example 53 was dissolved in ether, and cooled to 78 C. Zinc borohydride (Zn(BH.sub.4).sub.2) was slowly added thereto and the obtained product was stirred. When the reaction was completed, the obtained product was washed by H.sub.2O. The obtained organic layer was washed with H.sub.2O, dehydrated with anhydrous magnesium sulfate (MgSO.sub.4), filtrated, and concentrated under reduced pressure. The concentrated residue was purified by a silica gel column chromatography to produce the title compound (0.04 g, yield 2533%, cis:trans=2:1).

(166) .sup.1H NMR (400 MHz, CDCl.sub.3) 0.11 (s, 3H), 0.11 (s, 3H), 0.93 (S, 9H), 1.07 (d, J=6.4 3H), 2.05 (d, J=6.4 1H), 4.014.05 (m, 1H), 5.18 (d, J=4.0, 1H), 7.207.56 (m, 4H))

Preparation Example 55

Synthesis of 1-(2-chlorophenyl)-(R,S)-1,2-propanediol

(167) ##STR00066##

(168) 1-(2-chlorophenyl)-(R)-1-(t-butyldimethyl-siloxy)-(S)-2-propanol (10.38 g) obtained in Preparation Example 54 was dissolved in methanol (CH.sub.3OH, 100 ml), and then, cooled to 0 C. 8M hydrochloric acid (HCl, 56.2 ml) was slowly added in drop-wise manner to the obtained product, and then, the obtained product was warmed to the room temperature, and stirred for 15 hours. When the reaction was completed, the obtained product was cooled to 0 C. 5N sodium hydroxide (NaOH, 30 ml) was slowly added thereto, and the obtained product was subjected to vacuum concentration. The obtained product was diluted with ethylacetate. The obtained organic layer was washed with distilled water, dehydrated with anhydrous magnesium sulfate (MgSO.sub.4), filtrated, and concented under reduced pressure. The concentrated residue was purified by a silica gel column chromatography to produce the title compound (7.05 g, yield 6090%).

(169) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.07 (d, J=6.8, 3H), 2.01 (d, J=5.6, 1H), 2.61 (s, 1H), 4.214.27 (m, 1H), 5.24 (d, J=3.6, 1H), 7.227.64 (m, 4H)

Preparation Example 56

Synthesis of 1-(2-chlorophenyl)-(S,R)-1,2-propanediol

(170) ##STR00067##

(171) The substantially same method as described in Preparation Example 5055 was conducted, except that (S)-2-chloromandelic acid was used instead of (R)-2-chloromandelic acid, to obtain the title compound (5.04 g, yield 84%).

(172) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.07 (d, J=6.8, 3H), 2.00 (d, J=5.6, 1H), 2.54 (d, J=3.6, 1H), 4.224.26 (m, 1H), 5.25 (t, J=3.2, 1H), 7.227.65 (m, 4H)

Preparation Example 57

Synthesis of 1-(2,3-dichlorophenyl)-(S,S)-1,2-propanediol

(173) ##STR00068##

(174) The substantially same method as described in Preparation Example 14 was conducted, except that 1-(2,3-dichlorophenyl)-trans-1-propene (Preparation Example 13) was used instead of 1-(2-chlorophenyl)-trans-1-propene (Preparation Example 1), to obtain the title compound (0.9 g, yield 6090%).

(175) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.10 (d, J=6.4 Hz, 3H), 2.72 (d, J=2.4 Hz, 1H), 3.10 (d, J=8.4 Hz, 1H), 4.474.54 (m, 1H), 5.24 (t, J=8.8 Hz, 1H), 7.18 (m, 3H)

Preparation Example 58

Synthesis of 1-(2,3-dichlorophenyl)-(R,R)-1,2-propanediol

(176) ##STR00069##

(177) The substantially same method as described in Preparation Example 15 was conducted, except that 1-(2,3-dichlorophenyl)-trans-1-propene (Preparation Example 13) was used instead of 1-(2-chlorophenyl)-trans-1-propene (Preparation Example 1), to obtain the title compound (0.84 g, yield 6090%).

(178) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.10 (d, J=6.4 Hz, 3H), 2.72 (d, J=2.4 Hz, 1H), 3.10 (d, J=8.4 Hz, 1H), 4.474.54 (m, 1H), 5.24 (t, J=8.8 Hz, 1H), 7.18 (m, 3H)

Preparation Example 59

Synthesis of the mixture of 1-(2,3-dichlorophenyl)-(S,S)-1,2-propanediol and 1-(2,3-dichlorophenyl)-(R,R)-1,2-propanediol

(179) ##STR00070##

(180) The substantially same method as described in Preparation Example 16 was conducted, except that 1-(2,3-dichlorophenyl)-trans-1-propene (Preparation Example 13) was used instead of 1-(2-chlorophenyl)-trans-1-propene (Preparation Example 1), to obtain the title compound (0.91 g, yield 6090%).

(181) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.10 (d, J=6.4 Hz, 3H), 2.72 (d, J=2.4 Hz, 1H), 3.10 (d, J=8.4 Hz, 1H), 4.474.54 (m, 1H), 5.24 (t, J=8.8 Hz, 1H), 7.18(m, 3H)

Preparation Example 60

Synthesis of 1-(2-fluorophenyl)-trans-1-propene

(182) ##STR00071##

(183) The substantially same method as described in Preparation Example 1 was conducted, except that 2-fluorobenzenaldehyde was used instead of 2-chlorobenzenealdehyde, to obtain the title compound (6.67 g, yield 61%).

(184) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.94 (d, J=6.8 Hz, 3H), 6.306.38 (m, 1H), 6.57 (d, J=16 Hz, 1H), 7.007.41 (m, 4H)

Preparation Example 61

Synthesis of 1-(2-fluorophenyl)-(S,S)-1,2-propanediol

(185) ##STR00072##

(186) The substantially same method as described in Preparation Example 14 was conducted, except that 1-(2-fluorophenyl)-trans-1-propene (Preparation Example 60) was used instead of 1-(2-chlorophenyl)-trans-1-propene (Preparation Example 1), to obtain the title compound (6.46 g, yield 78%).

(187) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.15 (d, J=6.4 Hz, 3H), 2.43 (d, J=3.6 Hz, 1H), 2.69 (d, J=4.8 Hz, 1H), 3.903.98 (m, 1H), 4.78 (dd, J=4.4, 7.2 Hz, 1H), 7.047.50 (m, 4H)

Preparation Example 62

Synthesis of 1-(2-fluorophenyl)-(R,R)-1,2-propanediol

(188) ##STR00073##

(189) The substantially same method as described in Preparation Example 15 was conducted, except that 1-(2-fluorophenyl)-trans-1-propene (Preparation Example 60) was used instead of 1-(2-chlorophenyl)-trans-1-propene (Preparation Example 1), to obtain the title compound (3.29 g, yield 79%).

(190) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.15 (d, J=6.4 Hz, 3H), 2.43 (d, J=3.6 Hz, 1H), 2.69 (d, J=4.8 Hz, 1H), 3.903.98 (m, 1H), 4.78 (dd, J=4.4, 7.2 Hz, 1H), 7.047.50 (m, 4H)

Preparation Example 63

Synthesis of 2-iodobenzenealdehyde

(191) ##STR00074##

(192) In a flask, 2-iodobenzyl alcohol (4 g, 17.09 mmol) was dissolved in dichloromethane (MC, 85 ml), and then, manganese oxide (MnO.sub.2, 14.86 g, 170.92 mmol) was added thereto. The obtained reaction product was stirred under the reflux condition. When the reaction was completed, the obtained reaction product was cooled to the room temperature, and then, fiteated and concentrated using celite, to obtain the title compound (3.6 g, yield 91%).

(193) .sup.1H NMR (400 MHz, CDCl.sub.3) 7.307.99 (m, 4H), 10.10 (s, 1H)

Preparation Example 64

Synthesis of 1-(2-iodophenyl)-trans-1-propene

(194) ##STR00075##

(195) The substantially same method as described in Preparation Example 1 was conducted, except that 2-iodobenzenealdehyde (Preparation Example 63) was used instead of 2-chlorobenzenealdehyde, to obtain the title compound (3.4 g, yield 65%).

(196) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.95 (dd, J=6.8 Hz, 1.6 Hz, 3H), 6.096.18 (m, 1H), 6.60 (dd, J=15.66 Hz, 1.8 Hz, 1H), 6.897.84 (m, 4H)

Preparation Example 65

Synthesis of 1-(2-iodophenyl)-trans-1-butene

(197) ##STR00076##

(198) The substantially same method as described in Preparation Example 64 was conducted, except that 3-heptanone was used instead of 3-pentanone, to obtain the title compound (8.5 g, yield 75%).

(199) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.46 (t, J=7.6 Hz, 3H), 2.262.34 (m, 2H), 6.17 (dt, J=15.6 Hz, 6.6 Hz 1H), 6.57 (d, J=15.6 Hz, 1H), 6.897.85 (m, 4H)

Preparation Example 66

Synthesis of 1-(2-iodophenyl)-(S,S)-1,2-propanediol

(200) ##STR00077##

(201) The substantially same method as described in Preparation Example 14 was conducted, except that 1-(2-iodophenyl)-trans-1-propene (Preparation Example 64) was used instead of 1-(2-chlorophenyl)-trans-1-propene (Preparation Example 1), to obtain the title compound (3.4 g, yield 88%).

(202) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.27 (d, J=6.4 Hz, 3H), 2.26 (br s, 1H), 2.74 (br s, 1H), 3.99 (t, J=6.0 Hz, 1H), 4.81 (d, J=4.0 Hz, 1H), 7.017.87 (m, 4H)

Preparation Example 67

Synthesis of 1-(2-iodorophenyl)-(R,R)-1,2-propanediol

(203) ##STR00078##

(204) The substantially same method as described in Preparation Example 15 was conducted was conducted, except that 1-(2-iodophenyl)-trans-1-propene (Preparation Example 64) was used instead of 1-(2-chlorophenyl)-trans-1-propene (Preparation Example 1), to obtain the title compound (7.4 g, yield 84%).

(205) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.26 (d, J=6.4 Hz, 3H), 2.35 (br s, 1H), 2.85 (br d, J=4.0 Hz, 1H), 3.98 (t, J=6.2 Hz, 1H), 4.80 (dd, J=5.0, 4.4 Hz, 1H), 7.007.87 (m, 4H)

Preparation Example 68

Synthesis of 1-(2-iodophenyl)-(S,S)-1,2-butanediol

(206) ##STR00079##

(207) The substantially same method as described in Preparation Example 14 was conducted was conducted, except that 1-(2-iodophenyl)-trans-1-butene (Preparation Example 65) was used instead of 1-(2-chlorophenyl)-trans-1-propene (Preparation Example 1), to obtain the title compound (9.5 g, yield 84%).

(208) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.04 (t, J=7.6 Hz, 3H), 1.601.71 (m, 2H), 2.07 (br s, 1H), 2.74 (br s, 1H), 3.713.76 (m, 1H), 4.87 (d, J=4.8 Hz, 1H), 7.017.87 (m, 4H)

Preparation Example 69

Preparation of 1-(2-chlorophenyl)-(S,S)-1,2-(Bis-trimethylsilanyloxy) propane

(209) ##STR00080##

(210) To a stirred solution of 1-(2-chlorophenyl)-(S,S)-1,2-propanediol (Preparation example 14, 67 g, 0.35 mol) in CH.sub.2Cl.sub.2 (670 ml) was added Et.sub.3N (200 mL, 1.43 mol) and TMSCl (113.9 mL, 0.89 mol) at 0 C. under N.sub.2. The reaction mixture was allowed to stir at 0 C. for 3 hr. The reaction mixture was quenched with H.sub.2O (650 mL) at 0 C. The organic layer was separated and collected. The aqueous layer was extracted with CH.sub.2Cl.sub.2 (300 mL), dried over MgSO.sub.4. Concentration under vacuum provided a crude product. 104.18 g (117.44%).

(211) .sup.1H NMR (400 MHz, CDCl.sub.3) 0.053 (s, 9H), 0.044 (s, 9H), 1.15 (d, J=5.6 Hz, 3H), 3.9773.918 (m, 1H), 4.973 (d, J=6.4 Hz, 1H), 7.2077.165 (m, 1H), 7.3217.245 (m, 2H), 7.5667.543 (m, 1H)

Preparation Example 70

Preparation of 1-(2-chlorophenyl)-(R,R)-1,2-(Bis-trimethylsilanyloxy) propane

(212) ##STR00081##

(213) The substantially same method as described in Preparation Example 69 was conducted, except that 1-(2-chlorophenyl)-(R,R)-1,2-propanediol (Preparation example 15) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-propanediol (Preparation example 14) to obtain the title compound (8.5 g, yield 90120%).

(214) .sup.1H NMR (400 MHz, CDCl.sub.3) 0.053 (s, 9H), 0.044 (s, 9H), 1.15 (d, J=5.6 Hz, 3H), 3.9773.918 (m, 1H), 4.973 (d, J=6.4 Hz, 1H), 7.217.54 (m, 4H)

Preparation Example 71

Preparation of 1-(2-chlorophenyl)-1,2-(Bis-trimethylsilanyloxy) propane

(215) ##STR00082##

(216) The substantially same method as described in Preparation Example 69 was conducted, except that 1-(2-chlorophenyl)propane-1,2-diol (Preparation example 16) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-propanediol (Preparation example 14) to obtain the title compound (5.2 g, yield 90120%).

(217) .sup.1H NMR (400 MHz, CDCl.sub.3) 0.053 (s, 9H), 0.044 (s, 9H), 1.15 (d, J=5.6 Hz, 3H), 3.9773.918 (m, 1H), 4.973 (d, J=6.4 Hz, 1H), 7.217.54 (m, 4H)

Preparation Example 72

Preparation of 1-(2-chlorophenyl)-(S,R)-1,2-(Bis-trimethylsilanyloxy) propane

(218) ##STR00083##

(219) The substantially same method as described in Preparation Example 69 was conducted, except that 1-(2-chlorophenyl)-(S,R)-1,2-propanediol (Preparation example 56) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-propanediol (Preparation example 14) to obtain the title compound (3.4 g, yield 90120%).

(220) .sup.1H NMR (400 MHz, CDCl.sub.3) 0.053 (s, 9H), 0.044 (s, 9H), 1.15 (d, J=5.6 Hz, 3H), 3.9773.918 (m, 1H), 4.973 (d, J=6.4 Hz, 1H), 7.217.54 (m, 4H)

Preparation Example 73

Preparation of 1-(2-chlorophenyl)-(R,S)-1,2-(Bis-trimethylsilanyloxy) propane

(221) ##STR00084##

(222) The substantially same method as described in Preparation Example 69 was conducted, except that 1-(2-chlorophenyl)-(R,S)-1,2-propanediol (Preparation example 55) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-propanediol (Preparation example 14) to obtain the title compound (3.2 g, yield 90120%).

(223) .sup.1H NMR (400 MHz, CDCl.sub.3) 0.053 (s, 9H), 0.044 (s, 9H), 1.15 (d, J=5.6 Hz, 3H), 3.9773.918 (m, 1H), 4.973 (d, J=6.4 Hz, 1H), 7.217.54 (m, 4H)

Preparation Example 74

Preparation of 1-(2-chlorophenyl)-(S,S)-1,2-(Bis-trimethylsilanyloxy) butane

(224) ##STR00085##

(225) The substantially same method as described in Preparation Example 69 was conducted, except that 1-(2-chlorophenyl)-(S,S)-1,2-butanediol (Preparation example 17) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-propanediol (Preparation example 14) to obtain the title compound (3.6 g, yield 90120%).

(226) .sup.1H NMR (400 MHz, CDCl.sub.3) 0.053 (s, 9H), 0.044 (s, 9H), 1.01 (t, J=7.4 Hz, 3H), 1.521.65 (m, 2H), 3.693.75 (m, 1H), 5.05 (t, J=5.0 Hz, 1H), 7.237.54 (m, 4H)

Preparation Example 75

Preparation of 1-(2-chlorophenyl)-(R,R)-1,2-(Bis-trimethylsilanyloxy) butane

(227) ##STR00086##

(228) The substantially same method as described in Preparation Example 69 was conducted, except that 1-(2-chlorophenyl)-(R,R)-1,2-butanediol (Preparation example 18) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-propanediol (Preparation example 14) to obtain the title compound (3.5 g, yield 90120%).

(229) .sup.1H NMR (400 MHz, CDCl.sub.3) 0.053 (s, 9H), 0.044 (s, 9H), 1.01 (t, J=7.4 Hz, 3H), 1.521.65 (m, 2H), 3.693.75 (m, 1H), 5.05 (t, J=5.0 Hz, 1H), 7.237.54 (m, 4H)

Preparation Example 76

Preparation of 1-(2-chlorophenyl)-1,2-(Bis-trimethylsilanyloxy) butane

(230) ##STR00087##

(231) The substantially same method as described in Preparation Example 69 was conducted, except that 1-(2-chlorophenyl)-1,2-butanediol (Preparation example 19) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-propanediol (Preparation example 14) to obtain the title compound (3.0 g, yield 90120%).

(232) .sup.1H NMR (400 MHz, CDCl.sub.3) 0.053 (s, 9H), 0.044 (s, 9H), 1.01 (t, J=7.4 Hz, 3H), 1.521.65 (m, 2H), 3.693.75 (m, 1H), 5.05 (t, J=5.0 Hz, 1H), 7.237.54 (m, 4H)

Preparation Example 77

Preparation of 1-(2-chlorophenyl)-3-methyl-(S,S)-1,2-(Bis-trimethylsilanyloxy)-butane

(233) ##STR00088##

(234) The substantially same method as described in Preparation Example 69 was conducted, except that 1-(2-chlorophenyl)-3-methyl-(S,S)-1,2-butanediol (Preparation example 20) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-propanediol (Preparation example 14) to obtain the title (2.7 g, yield 90120%).

(235) .sup.1H NMR (400 MHz, CDCl.sub.3) 0.053 (s, 9H), 0.044 (s, 9H), 1.07 (t, J=7.2 Hz, 6H), 1.831.89 (m, 1H), 3.533.56 (m, 1H), 5.225.25 (m, 1H), 7.237.55 (m, 4H)

Preparation Example 78

Preparation of 1-(2-chlorophenyl)-3-methyl-(R,R)-1,2-(Bis-trimethylsilanyloxy)-butane

(236) ##STR00089##

(237) The substantially same method as described in Preparation Example 69 was conducted, except that 1-(2-chlorophenyl)-3-methyl-(R,R)-1,2-butanediol (Preparation example 21) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-propanediol (Preparation example 14) to obtain the title compound (2.4 g, yield 90120%).

(238) .sup.1H NMR (400 MHz, CDCl.sub.3) 0.053 (s, 9H), 0.044 (s, 9H), 1.07 (t, J=7.2 Hz, 6H), 1.831.89 (m, 1H), 3.533.56 (m, 1H), 5.225.25 (m, 1H), 7.237.55 (m, 4H)

Preparation Example 79

Preparation of 1-(2-chlorophenyl)-3-methyl-1,2-(Bis-trimethylsilanyloxy)-butane

(239) ##STR00090##

(240) The substantially same method as described in Preparation Example 69 was conducted, except that 1-(2-chlorophenyl)-3-methyl-1,2-butanediol (Preparation example 22) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-propanediol (Preparation example 14) to obtain the title compound (2.8 g, yield 90120%).

(241) .sup.1H NMR (400 MHz, CDCl.sub.3) 0.053 (s, 9H), 0.044 (s, 9H), 1.07 (t, J=7.2 Hz, 6H), 1.831.89 (m, 1H), 3.533.56 (m, 1H), 5.225.25 (m, 1H), 7.237.55 (m, 4H)

Preparation Example 80

Preparation of 1-(2-chlorophenyl)-(S,S)-1,2-(Bis-trimethylsilanyloxy)-hexane

(242) ##STR00091##

(243) The substantially same method as described in Preparation Example 69 was conducted, except that 1-(2-chlorophenyl)-(S,S)-1,2-hexanediol (Preparation example 23) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-propanediol (Preparation example 14) to obtain the title compound (3.1 g, yield 90120%).

(244) .sup.1H NMR (400 MHz, CDCl.sub.3) 0.053 (s, 9H), 0.044 (s, 9H), 0.90 (t, J=7.2 Hz, 3H), 1.351.65 (m, 6H), 3.783.83 (m, 1H), 5.04 (t, J=5.0 Hz, 1H), 7.237.53 (m, 4H)

Preparation Example 81

Preparation of 1-(2-chlorophenyl)-(S,S)-1,2-(Bis-trimethylsilanyloxy)-hexane

(245) ##STR00092##

(246) The substantially same method as described in Preparation Example 69 was conducted, except that 1-(2-chlorophenyl)-(R,R)-1,2-hexanediol (Preparation example 24) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-propanediol (Preparation example 14) to obtain the title compound (3.3 g, yield 90120%).

(247) .sup.1H NMR (400 MHz, CDCl.sub.3) 0.053 (s, 9H), 0.044 (s, 9H), 0.90 (t, J=7.2 Hz, 3H), 1.351.65 (m, 6H), 3.783.83 (m, 1H), 5.04 (t, J=5.0 Hz, 1H), 7.237.53 (m, 4H)

Preparation Example 82

Preparation of 1-(2-chlorophenyl)-(S,S)-1,2-(Bis-trimethylsilanyloxy)-hexane

(248) ##STR00093##

(249) The substantially same method as described in Preparation Example 69 was conducted, except that 1-(2-chlorophenyl)-1,2-hexanediol (Preparation example 25) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-propanediol (Preparation example 14) to obtain the title compound (3.2 g, yield 90120%).

(250) .sup.1H NMR (400 MHz, CDCl.sub.3) 0.053 (s, 9H), 0.044 (s, 9H), 0.90 (t, J=7.2 Hz, 3H), 1.351.65 (m, 6H), 3.783.83 (m, 1H), 5.04 (t, J=5.0 Hz, 1H), 7.237.53 (m, 4H)

Preparation Example 83

Preparation of 1-(2,4-dichlorophenyl)-(S,S)-1,2-(Bis-trimethylsilanyloxy)-propane

(251) ##STR00094##

(252) The substantially same method as described in Preparation Example 69 was conducted, except that 1-(2,4-dichlorophenyl)-(S,S)-1,2-propanediol (Preparation example 26) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-propanediol (Preparation example 14) to obtain the title compound (2.4 g, yield 90120%).

(253) .sup.1H NMR (400 MHz, CDCl.sub.3) 0.053 (s, 9H), 0.044 (s, 9H), 1.22 (d, J=6.4 Hz, 3H), 3.903.95 (m, 1H), 4.94 (t, J=5.0 Hz, 1H), 7.31 (dd, J=2.0 Hz, J=8.0 Hz, 1H), 7.40 (d, J=2.0 Hz, 1H), 7.49 (d, J=8.4 Hz, 1H)

Preparation Example 84

Preparation of 1-(2,6-dichlorophenyl)-(S,S)-1,2-(Bis-trimethylsilanyloxy)-propane

(254) ##STR00095##

(255) The substantially same method as described in Preparation Example 69 was conducted, except that 1-(2,6-dichlorophenyl)-(S,S)-1,2-propanediol (Preparation example 38) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-propanediol (Preparation example 14) to obtain the title compound (3.4 g, yield 90120%).

(256) .sup.1H NMR (400 MHz, CDCl.sub.3) 0.053 (s, 9H), 0.044 (s, 9H), 1.10 (d, J=6.4 Hz, 3H), 4.474.54 (m, 1H), 5.24 (t, J=8.8 Hz, 1H), 7.137.36 (m, 3H)

Preparation Example 85

Preparation of 1-(2,3-dichlorophenyl)-(S,S)-1,2-(Bis-trimethylsilanyloxy)-propane

(257) ##STR00096##

(258) The substantially same method as described in Preparation Example 69 was conducted, except that 1-(2,3-dichlorophenyl)-(S,S)-1,2-propanediol (Preparation example 57) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-propanediol (Preparation example 14) to obtain the title compound (2.2 g, yield 90120%).

(259) .sup.1H NMR (400 MHz, CDCl.sub.3) 0.053 (s, 9H), 0.044 (s, 9H), 1.10 (d, J=6.4 Hz, 3H), 4.474.54 (m, 1H), 5.24 (t, J=8.8 Hz, 1H), 7.187.22 (m, 3H)

Preparation Example 86

Preparation of 1-(2,4-dichlorophenyl)-(S,S)-1,2-(Bis-trimethylsilanyloxy)-butane

(260) ##STR00097##

(261) The substantially same method as described in Preparation Example 69 was conducted, except that 1-(2,4-dichlorophenyl)-(S,S)-1,2-butanediol (Preparation example 29) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-propanediol (Preparation example 14) to obtain the title compound (3.1 g, yield 90120%).

(262) .sup.1H NMR (400 MHz, CDCl.sub.3) 0.053 (s, 9H), 0.044 (s, 9H), 1.02 (t, J=7.4 Hz, 3H), 1.541.61 (m, 2H), 3.653.68 (m, 1H), 5.01 (t, J=5.0 Hz, 1H), 7.317.49 (m, 3H)

Preparation Example 87

Preparation of 1-(2,6-dichlorophenyl)-(S,S)-1,2-(Bis-trimethylsilanyloxy)-butane

(263) ##STR00098##

(264) The substantially same method as described in Preparation Example 69 was conducted, except that 1-(2,6-dichlorophenyl)-(S,S)-1,2-butanediol (Preparation example 41) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-propanediol (Preparation example 14) to obtain the title compound (2.8 g, yield 90120%).

(265) .sup.1H NMR (400 MHz, CDCl.sub.3) 0.053 (s, 9H), 0.044 (s, 9H), 0.97 (t, J=7.6 Hz, 3H), 1.261.53 (m, 2H), 4.224.26 (m, 1H), 5.26 (t, J=8.4 Hz, 1H), 7.177.35 (m, 3H)

Preparation Example 88

Preparation of 1-(2,4-dichlorophenyl)-3-methyl-(S,S)-1,2-(Bis-trimethylsilanyloxy)-butane

(266) ##STR00099##

(267) The substantially same method as described in Preparation Example 69 was conducted, except that 1-(2,4-dichlorophenyl)-3-methyl-(S,S)-1,2-butanediol (Preparation example 32) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-propanediol (Preparation example 14) to obtain the title compound (2.7 g, yield 90120%).

(268) .sup.1H NMR (400 MHz, CDCl.sub.3) 0.053 (s, 9H), 0.044 (s, 9H), 1.00 (d, J=6.8 Hz, 6H), 1.601.65 (m, 1H), 4.134.18 (m, 1H), 5.36 (t, J=7.6 Hz, 1H), 7.307.53 (m, 3H)

Preparation Example 89

Preparation of 1-(2,6-dichlorophenyl)-3-methyl-(S,S)-1,2-(Bis-trimethylsilanyloxy)-butane

(269) ##STR00100##

(270) The substantially same method as described in Preparation Example 69 was conducted, except that 1-(2,6-dichlorophenyl)-3-methyl-(S,S)-1,2-butanediol (Preparation example 44) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-propanediol (Preparation example 14) to obtain the title compound (3.3 g, yield 90120%).

(271) .sup.1H NMR (400 MHz, CDCl.sub.3) 0.053 (s, 9H), 0.044 (s, 9H), 1.00 (d, J=6.8 Hz, 6H), 1.601.65 (m, 1H), 4.134.18 (m, 1H), 5.36 (t, J=7.6 Hz, 1H), 7.177.35 (m, 3H)

Preparation Example 90

Preparation of 1-(2,4-dichlorophenyl)-(S,S)-1,2-(Bis-trimethylsilanyloxy)-hexane

(272) ##STR00101##

(273) The substantially same method as described in Preparation Example 69 was conducted, except that 1-(2,4-dichlorophenyl)-(S,S)-1,2-hexanediol (Preparation example 90) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-propanediol (Preparation example 14) to obtain the title compound (3.6 g, yield 90120%).

(274) .sup.1H NMR (400 MHz, CDCl.sub.3) 0.053 (s, 9H), 0.044 (s, 9H), 0.890.93 (m, 3H), 1.301.39 (m, 2H), 1.491.52 (m, 2H), 1.561.6 (m, 2H), 3.723.77 (m, 1H), 4.98 (t, J=4.8 Hz, 1H), 7.287.50 (m, 3H)

Preparation Example 91

Preparation of 1-(2,6-dichlorophenyl)-(S,S)-1,2-(Bis-trimethylsilanyloxy)-hexane

(275) ##STR00102##

(276) The substantially same method as described in Preparation Example 69 was conducted, except that 1-(2,6-dichlorophenyl)-(S,S)-1,2-hexanediol (Preparation example 47) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-propanediol (Preparation example 14) to obtain the title compound (2.8 g, yield 90120%).

(277) .sup.1H NMR (400 MHz, CDCl.sub.3) 0.053 (s, 9H), 0.044 (s, 9H), 0.85 (t, J=6.7 Hz, 3H), 1.201.31 (m, 4H), 1.451.53 (m, 2H), 4.284.33 (m, 1H), 5.25 (t, J=8.4 Hz, 1H), 7.187.35 (m, 3H)

Preparation Example 92

Preparation of 1-(2,4-dichlorophenyl)-(R,R)-1,2-(Bis-trimethylsilanyloxy)-propane

(278) ##STR00103##

(279) The substantially same method as described in Preparation Example 69 was conducted, except that 1-(2,4-dichlorophenyl)-(R,R)-1,2-propanediol (Preparation example 27) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-propanediol (Preparation example 14) to obtain the title compound (2.2 g, yield 90120%).

(280) .sup.1H NMR (400 MHz, CDCl.sub.3) 0.053 (s, 9H), 0.044 (s, 9H), 1.22 (d, J=6.4 Hz, 3H), 3.903.95 (m, 1H), 4.94 (t, J=5.0 Hz, 1H), 7.317.49 (m, 3H)

Preparation Example 93

Preparation of 1-(2,6-dichlorophenyl)-(R,R)-1,2-(Bis-trimethylsilanyloxy)-propane

(281) ##STR00104##

(282) The substantially same method as described in Preparation Example 69 was conducted, except that 1-(2,6-dichlorophenyl)-(R,R)-1,2-propanediol (Preparation example 39) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-propanediol (Preparation example 14) to obtain the title compound (2.6 g, yield 90120%).

(283) .sup.1H NMR (400 MHz, CDCl.sub.3) 0.053 (s, 9H), 0.044 (s, 9H), 1.10 (d, J=6.4 Hz, 3H), 4.474.54 (m, 1H), 5.24 (t, J=8.8 Hz, 1H), 7.187.36 (m, 3H)

Preparation Example 94

Preparation of 1-(2,3-dichlorophenyl)-(R,R)-1,2-(Bis-trimethylsilanyloxy)-propane

(284) ##STR00105##

(285) The substantially same method as described in Preparation Example 69 was conducted, except that 1-(2,3-dichlorophenyl)-(R,R)-1,2-propanediol (Preparation example 58) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-propanediol (Preparation example 14) to obtain the title compound (2.9 g, yield 90120%).

(286) .sup.1H NMR (400 MHz, CDCl.sub.3) 0.053 (s, 9H), 0.044 (s, 9H), 1.10 (d, J=6.4 Hz, 3H), 4.474.54 (m, 1H), 5.24 (t, J=8.8 Hz, 1H), 7.187.22 (m, 3H)

Preparation Example 95

Preparation of 1-(2,4-dichlorophenyl)-(R,R)-1,2-(Bis-trimethylsilanyloxy)-butane

(287) ##STR00106##

(288) The substantially same method as described in Preparation Example 69 was conducted, except that 1-(2,4-dichlorophenyl)-(R,R)-1,2-butanediol (Preparation example 30) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-propanediol (Preparation example 14) to obtain the title compound (3.6 g, yield 90120%).

(289) .sup.1H NMR (400 MHz, CDCl.sub.3) 0.053 (s, 9H), 0.044 (s, 9H), 1.02 (t, J=7.4 Hz, 3H), 1.541.61 (m, 2H), 3.653.68 (m, 1H), 5.01 (t, J=5.0 Hz, 1H), 7.317.49 (m, 3H)

Preparation Example 96

Preparation of 1-(2,6-dichlorophenyl)-(R,R)-1,2-(Bis-trimethylsilanyloxy)-butane

(290) ##STR00107##

(291) The substantially same method as described in Preparation Example 69 was conducted, except that 1-(2,6-dichlorophenyl)-(R,R)-1,2-butanediol (Preparation example 42) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-propanediol (Preparation example 14) to obtain the title compound (3.3 g, yield 90120%).

(292) .sup.1H NMR (400 MHz, CDCl.sub.3) 0.053 (s, 9H), 0.044 (s, 9H), 0.97 (t, J=7.6 Hz, 3H), 1.261.53 (m, 2H), 4.224.26 (m, 1H), 5.26 (t, J=8.4 Hz, 1H), 7.177.35 (m, 3H)

Preparation Example 97

Preparation of 1-(2,4-dichlorophenyl)-3-methyl-(R,R)-1,2-(Bis-trimethylsilanyloxy)-butane

(293) ##STR00108##

(294) The substantially same method as described in Preparation Example 69 was conducted, except that 1-(2,4-dichlorophenyl)-3-methyl-(R,R)-1,2-butanediol (Preparation example 33) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-propanediol (Preparation example 14) to obtain the title compound (3.5 g, yield 90120%).

(295) .sup.1H NMR (400 MHz, CDCl.sub.3) 0.053 (s, 9H), 0.044 (s, 9H), 1.00 (d, J=6.8 Hz, 6H), 1.601.65 (m, 1H), 4.134.18 (m, 1H), 5.36 (t, J=7.6 Hz, 1H), 7.307.53 (m, 3H)

Preparation Example 98

Preparation of 1-(2,6-dichlorophenyl)-3-methyl-(R,R)-1,2-(Bis-trimethylsilanyloxy)-butane

(296) ##STR00109##

(297) The substantially same method as described in Preparation Example 69 was conducted, except that 1-(2,6-dichlorophenyl)-3-methyl-(R,R)-1,2-butanediol (Preparation example 45) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-propanediol (Preparation example 14) to obtain the title compound (3.4 g, yield 90120%).

(298) .sup.1H NMR (400 MHz, CDCl.sub.3) 0.053 (s, 9H), 0.044 (s, 9H), 1.00 (d, J=6.8 Hz, 6H), 1.601.65 (m, 1H), 4.134.18 (m, 1H), 5.36 (t, J=7.6 Hz, 1H), 7.177.35 (m, 3H)

Preparation Example 99

Preparation of 1-(2,4-dichlorophenyl)-(R,R)-1,2-(Bis-trimethylsilanyloxy)-hexane

(299) ##STR00110##

(300) The substantially same method as described in Preparation Example 69 was conducted, except that 1-(2,4-dichlorophenyl)-(R,R)-1,2-hexanediol (Preparation example 36) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-propanediol (Preparation example 14) to obtain the title compound (3.6 g, yield 90120%).

(301) .sup.1H NMR (400 MHz, CDCl.sub.3) 0.053 (s, 9H), 0.044 (s, 9H), 0.890.93 (m, 3H), 1.301.39 (m, 2H), 1.491.52 (m, 2H), 1.561.62 (m, 2H), 3.723.77 (m, 1H), 4.98 (t, J=4.8 Hz, 1H), 7.287.50 (m, 3H)

Preparation Example 100

Preparation of 1-(2,6-dichlorophenyl)-(R,R)-1,2-(Bis-trimethylsilanyloxy)-hexane

(302) ##STR00111##

(303) The substantially same method as described in Preparation Example 69 was conducted, except that 1-(2,6-dichlorophenyl)-(R,R)-1,2-hexanediol (Preparation example 48) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-propanediol (Preparation example 14) to obtain the title compound (3.3 g, yield 90120%).

(304) .sup.1H NMR (400 MHz, CDCl.sub.3) 0.053 (s, 9H), 0.044 (s, 9H), 0.85 (t, J=6.7 Hz, 3H), 1.201.31 (m, 4H), 1.451.53 (m, 2H), 4.284.33 (m, 1H), 5.25 (t, J=8.4 Hz, 1H), 7.187.35 (m, 3H)

Preparation Example 101

Preparation of 1-(2,4-dichlorophenyl)-1,2-(Bis-trimethylsilanyloxy)-propane

(305) ##STR00112##

(306) The substantially same method as described in Preparation Example 69 was conducted, except that 1-(2,4-dichlorophenyl)-1,2-propanediol (Preparation example 28) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-propanediol (Preparation example 14) to obtain the title compound (2.6 g, yield 90120%).

(307) .sup.1H NMR (400 MHz, CDCl.sub.3) 0.053 (s, 9H), 0.044 (s, 9H), 1.22 (d, J=6.4 Hz, 3H), 3.903.95 (m, 1H), 4.94 (t, J=5.0 Hz, 1H), 7.317.49 (m, 3H)

Preparation Example 102

Preparation of 1-(2,6-dichlorophenyl)-1,2-(Bis-trimethylsilanyloxy)-propane

(308) ##STR00113##

(309) The substantially same method as described in Preparation Example 69 was conducted, except that 1-(2,6-dichlorophenyl)-1,2-propanediol (Preparation example 40) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-propanediol (Preparation example 14) to obtain the title compound (3.1 g, yield 90120%).

(310) .sup.1H NMR (400 MHz, CDCl.sub.3) 0.053 (s, 9H), 0.044 (s, 9H), 1.10 (d, J=6.4 Hz, 3H), 4.474.54 (m, 1H), 5.24 (t, J=8.8 Hz, 1H), 7.187.36 (m, 3H)

Preparation Example 103

Preparation of 1-(2,3-dichlorophenyl)-1,2-(Bis-trimethylsilanyloxy)-propane

(311) ##STR00114##

(312) The substantially same method as described in Preparation Example 69 was conducted, except that 1-(2,3-dichlorophenyl)-1,2-propanediol (Preparation example 59) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-propanediol (Preparation example 14) to obtain the title compound (2.7 g, yield 90120%).

(313) .sup.1H NMR (400 MHz, CDCl.sub.3) 0.053 (s, 9H), 0.044 (s, 9H), 1.10 (d, J=6.4 Hz, 3H), 4.474.54 (m, 1H), 5.24 (t, J=8.8 Hz, 1H), 7.187.22 (m, 3H)

Preparation Example 104

Preparation of 1-(2,4-dichlorophenyl)-1,2-(Bis-trimethylsilanyloxy)-butane

(314) ##STR00115##

(315) The substantially same method as described in Preparation Example 69 was conducted, except that 1-(2,4-dichlorophenyl)-1,2-butanediol (Preparation example 31) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-propanediol (Preparation example 14) to obtain the title compound (2.9 g, yield 90120%).

(316) .sup.1H NMR (400 MHz, CDCl.sub.3) 0.053 (s, 9H), 0.044 (s, 9H), 1.02 (t, J=7.4 Hz, 3H), 1.541.61 (m, 2H), 3.653.68 (m, 1H), 5.01 (t, J=5.0 Hz, 1H), 7.317.49 (m, 3H)

Preparation Example 105

Preparation of 1-(2,6-dichlorophenyl)-1,2-(Bis-trimethylsilanyloxy)-butane

(317) ##STR00116##

(318) The substantially same method as described in Preparation Example 69 was conducted, except that 1-(2,6-dichlorophenyl)-1,2-butanediol (Preparation example 43) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-propanediol (Preparation example 14) to obtain the title compound (3.1 g, yield 90120%).

(319) .sup.1H NMR (400 MHz, CDCl.sub.3) 0.053 (s, 9H), 0.044 (s, 9H), 0.97 (t, J=7.6 Hz, 3H), 1.261.53 (m, 2H), 4.224.26 (m, 1H), 5.26 (t, J=8.4 Hz, 1H), 7.177.35 (m, 3H)

Preparation Example 106

Preparation of 1-(2,4-dichlorophenyl)-3-methyl-1,2-(Bis-trimethylsilanyloxy)-butane

(320) ##STR00117##

(321) The substantially same method as described in Preparation Example 69 was conducted, except that 1-(2,4-dichlorophenyl)-3-methyl-1,2-butanediol (Preparation example 34) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-propanediol (Preparation example 14) to obtain the title compound (2.7 g, yield 90120%).

(322) .sup.1H NMR (400 MHz, CDCl.sub.3) 0.053 (s, 9H), 0.044 (s, 9H), 1.00 (d, J=6.8 Hz, 6H), 1.601.65 (m, 1H), 4.134.18 (m, 1H), 5.36 (t, J=7.6 Hz, 1H), 7.307.53 (m, 3H)

Preparation Example 107

Preparation of 1-(2,6-dichlorophenyl)-3-methyl-1,2-(Bis-trimethylsilanyloxy)-butane

(323) ##STR00118##

(324) The substantially same method as described in Preparation Example 69 was conducted, except that 1-(2,6-dichlorophenyl)-3-methyl-1,2-butanediol (Preparation example 46) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-propanediol (Preparation example 14) to obtain the title compound (2.6 g, yield 90120%).

(325) .sup.1H NMR (400 MHz, CDCl.sub.3) 0.053 (s, 9H), 0.044 (s, 9H), 1.00 (d, J=6.8 Hz, 6H), 1.601.65 (m, 1H), 4.134.18 (m, 1H), 5.36 (t, J=7.6 Hz, 1H), 7.177.35 (m, 3H)

Preparation Example 108

Preparation of 1-(2,4-dichlorophenyl)-1,2-(Bis-trimethylsilanyloxy)-hexane

(326) ##STR00119##

(327) The substantially same method as described in Preparation Example 69 was conducted, except that 1-(2,4-dichlorophenyl)-1,2-hexanediol (Preparation example 37) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-propanediol (Preparation example 14) to obtain the title compound (3.7 g, yield 90120%).

(328) .sup.1H NMR (400 MHz, CDCl.sub.3) 0.053 (s, 9H), 0.044 (s, 9H), 0.890.93 (m, 3H), 1.301.39 (m, 2H), 1.491.52 (m, 2H), 1.561.62 (m, 2H), 3.723.77 (m, 1H), 4.98 (t, J=4.8 Hz, 1H), 7.287.50 (m, 3H)

Preparation Example 109

Preparation of 1-(2,6-dichlorophenyl)-1,2-(Bis-trimethylsilanyloxy)-hexane

(329) ##STR00120##

(330) The substantially same method as described in Preparation Example 69 was conducted, except that 1-(2,6-dichlorophenyl)-1,2-hexanediol (Preparation example 49) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-propanediol (Preparation example 14) to obtain the title compound (3.2 g, yield 90120%).

(331) .sup.1H NMR (400 MHz, CDCl.sub.3) 0.053 (s, 9H), 0.044 (s, 9H), 0.85 (t, J=6.7 Hz, 3H), 1.201.31 (m, 4H), 1.451.53 (m, 2H), 4.284.33 (m, 1H), 5.25 (t, J=8.4 Hz, 1H), 7.187.35 (m, 3H)

Preparation Example 110

Preparation of 1-(2-fluorophenyl)-(S,S)-1,2-(Bis-trimethylsilanyloxy)-propane

(332) ##STR00121##

(333) The substantially same method as described in Preparation Example 69 was conducted, except that 1-(2-fluorophenyl)-(S,S)-1,2-propanediol (Preparation example 61) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-propanediol (Preparation example 14) to obtain the title compound (2.8 g, yield 90120%).

(334) .sup.1H NMR (400 MHz, CDCl.sub.3) 0.053 (s, 9H), 0.044 (s, 9H), 1.15 (d, J=6.4 Hz, 3H), 3.903.98 (m, 1H), 4.78 (dd, J=4.4, 7.2 Hz, 1H), 7.047.50 (m, 4H)

Preparation Example 111

Preparation of 1-(2-fluorophenyl)-(R,R)-1,2-(Bis-trimethylsilanyloxy)-propane

(335) ##STR00122##

(336) The substantially same method as described in Preparation Example 69 was conducted, except that 1-(2-fluorophenyl)-(R,R)-1,2-propanediol (Preparation example 62) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-propanediol (Preparation example 14) to obtain the title compound (2.5 g, yield 90120%).

(337) .sup.1H NMR (400 MHz, CDCl.sub.3) 0.053 (s, 9H), 0.044 (s, 9H), 1.15 (d, J=6.4 Hz, 3H), 3.903.98 (m, 1H), 4.78 (dd, J=4.4, 7.2 Hz, 1H), 7.047.50 (m, 4H)

Preparation Example 112

Preparation of 1-(2-iodophenyl)-(S,S)-1,2-(Bis-trimethylsilanyloxy)-propane

(338) ##STR00123##

(339) The substantially same method as described in Preparation Example 69 was conducted, except that 1-(2-iodophenyl)-(S,S)-1,2-propanediol (Preparation example 66) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-propanediol (Preparation example 14) to obtain the title compound (3.1 g, yield 90120%).

(340) .sup.1H NMR (400 MHz, CDCl.sub.3) 0.053 (s, 9H), 0.044 (s, 9H), 1.27 (d, J=6.4 Hz, 3H), 3.99 (t, J=6.0 Hz, 1H), 4.81 (d, J=4.0 Hz, 1H), 7.017.87 (m, 4H)

Preparation Example 113

Preparation of 1-(2-iodophenyl)-(R,R)-1,2-(Bis-trimethylsilanyloxy)-propane

(341) ##STR00124##

(342) The substantially same method as described in Preparation Example 69 was conducted, except that 1-(2-iodophenyl)-(R,R)-1,2-propanediol (Preparation example 67) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-propanediol (Preparation example 14) to obtain the title compound (2.8 g, yield 90120%).

(343) .sup.1H NMR (400 MHz, CDCl.sub.3) 0.053 (s, 9H), 0.044 (s, 9H), 1.26 (d, J=6.4 Hz, 3H), 3.98 (t, J=6.2 Hz, 1H), 4.88 (d, J=4.4 Hz, 1H), 7.007.87 (m, 4H)

Preparation Example 114

Preparation of 1-(2-iodophenyl)-(S,S)-1,2-(Bis-trimethylsilanyloxy)-butane

(344) ##STR00125##

(345) The substantially same method as described in Preparation Example 69 was conducted, except that 1-(2-iodophenyl)-(S,S)-1,2-butanediol (Preparation example 68) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-propanediol (Preparation example 14) to obtain the title compound (3.3 g, yield 90120%).

(346) .sup.1H NMR (400 MHz, CDCl.sub.3) 0.053 (s, 9H), 0.044 (s, 9H), 1.04 (t, J=7.6 Hz, 3H), 1.601.71 (m, 2H), 3.713.76 (m, 1H), 4.87 (d, J=4.8 Hz, 1H), 7.017.87 (m, 4H)

Example 1

Preparation of 1-(2-chlorophenyl)-(S)-1-hydroxypropyl-(S)-2-carbamate (1)

(347) ##STR00126##

(348) To a stirred solution of crude 1-(2-chlorophenyl)-(S,S)-1,2-(Bis-trimethylsilanyloxy) propane (preparation example 69, 104 g, 0.31 mol) in toluene (670 mL) was added by Chlorosulfonyl isocynate (62.5 mL, 0.71 mol) at 0 C. The reaction mixture was stirred for 2 hr. The reaction mixture was quenched with ice water and then was stirred by additional cold H.sub.2O (500 mL) for 2 hr. After separation of organic layer, the aqueous was adjusted pH23 with sat. NaHCO.sub.3 (400 mL) and extracted with EtOAc (300 mL3). The EtOAc layer was washed with sat. NaHCO.sub.3 (500 mL) and H.sub.2O (500 mL). The organic phase was treated with Charcoal for 1.5 hr. The organic phase was filtered with Cellite, dried over MgSO.sub.4. Filterion and concentration under vacuum provided the title compound of white solid (yield 85% (71.1 g), ee=99.9% MP=8384 C., [].sub.D=+57.8 (c=0.25, MeOH))

(349) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.24 (d, J=6.4, 3H), 2.91 (d, J=4.8, 1H), 4.68 (br s, 2H), 5.065.09 (m, 1H), 5.185.21 (m, 1H), 7.237.39 (m, 3H), 7.55 (dd, J=1.6, J=7.8, 1H)

(350) .sup.13C NMR (100 MHz, CDCl.sub.3) 16.4, 73.1, 75.0, 127.0, 128.4, 129.1, 129.5, 132.7, 138.0, 156.6

Example 2

Preparation of 1-(2-chlorophenyl)-(R)-1-hydroxypropyl-(R)-2-carbamate (2)

(351) ##STR00127##

(352) The substantially same method as described in Example 1 was conducted, except that 1-(2-chlorophenyl)-(R,R)-1,2-(Bis-trimethylsilanyloxy) propane (Preparation example 70) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-(Bis-trimethylsilanyloxy) propane (Preparation example 69) to obtain the title compound (5.7 g, yield 6090%).

(353) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.24 (d, J=6.4, 3H), 2.91 (d, J=4.8, 1H), 4.68 (br s, 2H), 5.065.09 (m, 1H), 5.185.21 (m, 1H), 7.237.39 (m, 3H), 7.55 (dd, J=1.6, J=7.8, 1H)

Example 3

Preparation of 1-(2-chlorophenyl)-1-hydroxypropyl-2-carbamate (3)

(354) ##STR00128##

(355) The substantially same method as described in Example 1 was conducted, except that 1-(2-chlorophenyl)-1,2-(Bis-trimethylsilanyloxy) propane (Preparation example 71) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-(Bis-trimethylsilanyloxy) propane (Preparation example 69) to obtain the title compound (3.8 g, yield 6090%).

(356) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.24 (d, J=6.4, 3H), 2.91 (d, J=4.8, 1H), 4.68 (br s, 2H), 5.065.09 (m, 1H), 5.185.21 (m, 1H), 7.237.39 (m, 3H), 7.55 (dd, J=1.6, J=7.8, 1H)

Example 4

Preparation of 1-(2-chlorophenyl)-(S)-1-hydroxypropyl-(R)-2-carbamate (4)

(357) ##STR00129##

(358) The substantially same method as described in Example 1 was conducted, except that 1-(2-chlorophenyl)-(S,R)-1,2-(Bis-trimethylsilanyloxy) propane (Preparation example 72) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-(Bis-trimethylsilanyloxy) propane (Preparation example 69) to obtain the title compound (2.4 g, yield 6090%).

(359) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.24 (d, J=6.4, 3H), 2.91 (d, J=4.8, 1H), 4.68 (br s, 2H), 5.065.09 (m, 1H), 5.185.21 (m, 1H), 7.237.39 (m, 3H), 7.55 (dd, J=1.6, J=7.8, 1H)

Example 5

Preparation of 1-(2-chlorophenyl)-(R)-1-hydroxypropyl-(S)-2-carbamate (5)

(360) ##STR00130##

(361) The substantially same method as described in Example 1 was conducted, except that 1-(2-chlorophenyl)-(R,S)-1,2-(Bis-trimethylsilanyloxy) propane (Preparation example 73) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-(Bis-trimethylsilanyloxy) propane (Preparation example 69) to obtain the title compound (2.3 g, yield 6090%).

(362) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.24 (d, J=6.4, 3H), 2.91 (d, J=4.8, 1H), 4.68 (br s, 2H), 5.065.09 (m, 1H), 5.185.21 (m, 1H), 7.237.39 (m, 3H), 7.55 (dd, J=1.6, J=7.8, 1H)

Example 6

Preparation of 1-(2-chlorophenyl)-(S)-1-hydroxybutyl-(S)-2-carbamate (6)

(363) ##STR00131##

(364) The substantially same method as described in Example 1 was conducted, except that 1-(2-chlorophenyl)-(S,S)-1,2-(Bis-trimethylsilanyloxy)butane (Preparation example 74) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-(Bis-trimethylsilanyloxy) propane (Preparation example 69) to obtain the title compound (2.6 g, yield 6090%).

(365) .sup.1H NMR (400 MHz, CDCl.sub.3) 0.96 (t, J=7.4 Hz, 3H), 1.571.73 (m, 2H), 3.01 (d, J=5.6 Hz, 1H), 4.74 (br s, 2H), 4.95 (dt, J=7.2, 8.8 Hz, 1H), 5.23 (t, J=5.6 Hz, 1H), 7.227.54 (m, 4H)

Example 7

Synthesis of 1-(2-chlorophenyl)-(R)-1-hydroxybutyl-(R)-2-carbamate (7)

(366) ##STR00132##

(367) The substantially same method as described in Example 1 was conducted, except that 1-(2-chlorophenyl)-(R,R)-1,2-(Bis-trimethylsilanyloxy)butane (Preparation Example 75) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-(Bis-trimethylsilanyloxy) propane (Preparation example 69) to obtain the title compound (2.5 g, yield 6090%).

(368) .sup.1H NMR (400 MHz, CDCl.sub.3) 0.94 (t, J=7.4 Hz, 3H), 1.531.73 (m, 2H), 2.92 (s, 1H), 4.78 (br s, 2H), 4.914.96 (m, 1H), 5.22 (d, J=5.5 Hz, 1H), 7.207.54 (m, 4H)

Example 8

Synthesis of 1-(2-chlorophenyl)-1-hydroxybutyl-2-carbamate (8)

(369) ##STR00133##

(370) The substantially same method as described in Example 1 was conducted, except that 1-(2-chlorophenyl)-1,2-(Bis-trimethylsilanyloxy)butane (Preparation Example 76) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-(Bis-trimethylsilanyloxy) propane (Preparation example 69) to obtain the title compound (1.9 g, yield 6090%).

(371) .sup.1H NMR (400 MHz, CDCl.sub.3) 0.97 (t, J=7 Hz, 3H), 1.581.74 (m, 2H), 2.94 (d, J=6 Hz, 1H), 4.69 (br s, 2H), 4.944.99 (m, 1H), 5.24 (t, J=6 Hz, 1H), 7.237.56 (m, 4H)

Example 9

Synthesis of 1-(2-chlorophenyl)-(S)-1-hydroxy-3-methyl-butyl-(S)-2-carbamate (9)

(372) ##STR00134##

(373) The substantially same method as described in Example 1 was conducted, except that 1-(2-chlorophenyl)-3-methyl-(S,S)-1,2-(Bis-trimethylsilanyloxy)butane (Preparation Example 77) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-(Bis-trimethylsilanyloxy) propane (Preparation example 69) to obtain the title compound (1.7 g, yield 6090%).

(374) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.01 (d, J=6.4 Hz, 3H), 1.09 (d, J=6.8 Hz, 3H), 2.06 (m, 1H), 2.75 (d, J=6.8 Hz, 1H), 4.58 (br s, 2H), 4.854.88 (m, 1H), 5.345.37 (m, 1H), 7.227.33 (m, 2H), 7.357.37 (m, 1H), 7.517.53 (m, 1H)

Example 10

Synthesis of 1-(2-chlorophenyl)-(R)-1-hydroxy-3-methyl-butyl-(R)-2-carbamate (10)

(375) ##STR00135##

(376) The substantially same method as described in Example 1 was conducted, except that 1-(2-chlorophenyl)-3-methyl-(R,R)-1,2-(Bis-trimethylsilanyloxy)butane (Preparation Example 78) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-(Bis-trimethylsilanyloxy) propane (Preparation example 69) to obtain the title compound (1.6 g, yield 6090%).

(377) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.01 (d, J=6.8 Hz, 3H), 1.09 (d, J=6.8 Hz, 3H), 2.06 (m, 1H), 2.73 (d, J=6.8 Hz, 1H), 4.57 (br s, 2H), 4.854.88 (m, 1H), 5.345.37 (m, 1H), 7.247.30 (m, 2H), 7.357.37 (m, 1H), 7.517.53 (m, 1H)

Example 11

Synthesis of 1-(2-chlorophenyl)-1-hydroxy-3-methyl-butyl-2-carbamate (11)

(378) ##STR00136##

(379) The substantially same method as described in Example 1 was conducted, except that 1-(2-chlorophenyl)-3-methyl-1,2-(Bis-trimethylsilanyloxy)butane (Preparation Example 79) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-(Bis-trimethylsilanyloxy) propane (Preparation example 69) to obtain the title compound (1.7 g, yield 6090%).

(380) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.00 (d, J=6.4 Hz, 3H), 1.09 (d, J=6.4 Hz, 3H), 2.08 (m, 1H), 2.76 (d, J=6.0 Hz, 1H), 4.59 (br s, 2H), 4.87 (dd, J=7.2 Hz, 4.4 Hz, 1H), 5.36 (t, J=4.6, 1H), 7.237.54 (m, 4H)

Example 12

Synthesis of 1-(2-chlorophenyl)-(S)-1-hydroxyhexyl-(S)-2-carbamate (12)

(381) ##STR00137##

(382) The substantially same method as described in Example 1 was conducted, except that 1-(2-chlorophenyl)-(S,S)-1,2-(Bis-trimethylsilanyloxy)hexane (Preparation Example 80) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-(Bis-trimethylsilanyloxy) propane (Preparation example 69) to obtain the title compound (2.3 g, yield 6090%).

(383) .sup.1H NMR (400 MHz, CDCl.sub.3) 0.88 (t, J=7 Hz, 3H), 1.331.42 (m, 4H), 1.531.71 (m, 2H), 2.89 (d, J=5.6 Hz, 1H) 4.64 (br s, 2H), 5.04 (dt, J=5.0, 9.0 Hz, 1H), 5.20 (t, J=5.6 Hz, 1H), 7.237.55 (m, 4H)

Example 13

Synthesis of 1-(2-chlorophenyl)-(R)-1-hydroxyhexyl-(R)-2-carbamate (13)

(384) ##STR00138##

(385) The substantially same method as described in Example 1 was conducted, except that 1-(2-chlorophenyl)-(R,R)-1,2-(Bis-trimethylsilanyloxy)hexane (Preparation Example 81) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-(Bis-trimethylsilanyloxy) propane (Preparation example 69) to obtain the title compound (2.2 g, yield 6090%).

(386) .sup.1H NMR (400 MHz, CDCl.sub.3) 0.89 (dd, J=5 Hz, 3H), 1.281.43 (m, 4H), 1.521.58 (m, 1H), 1.651.72 (m, 1H), 2.90 (d, J=6 Hz, 1H), 4.64 (br s, 2H), 5.015.06 (m, 1H), 5.22 (t, J=6 Hz, 1H), 7.227.56 (m, 4H)

Example 14

Synthesis of 1-(2-chlorophenyl)-1-hydroxyhexyl-2-carbamate (14)

(387) ##STR00139##

(388) The substantially same method as described in Example 1 was conducted, except that 1-(2-chlorophenyl)-1,2-(Bis-trimethylsilanyloxy)hexane (Preparation Example 82) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-(Bis-trimethylsilanyloxy) propane (Preparation example 69) to obtain the title compound (2.1 g, yield 6090%).

(389) .sup.1H NMR (400 MHz, CDCl.sub.3) 0.88 (dd, J=5 Hz, 3H), 1.311.43 (m, 4H), 1.631.70 (m, 1H), 1.521.60 (m, 1H), 3.06 (d, J=6 Hz, 1H), 4.75 (br s, 2H), 5.005.05 (m, 1H), 5.21 (t, J=6 Hz, 1H), 7.227.55 (m, 4H)

Example 15

Synthesis of 1-(2-chlorophenyl)-(S)-1-hydroxypropyl-(S)-2-N-methylcarbamate (15)

(390) ##STR00140##

(391) 1-(2-chlorophenyl)-(S,S)-1,2-propanediol (2.4 g) obtained in Preparation Example 14, tetrahydrofuran (THF, 12 ml), and carbonyldiimidazole (CDI, 3.12 g) were put into a flask and stirred at the room temperature. After approximately 3 hours, methylamine solution (CH.sub.3NH.sub.2, 4 ml (33% in EtOH)) was added thereto. When the reaction was completed, the obtained product was washed with 1M HCl solution and ethylacetate (EA). The separated organic layer was dehydrated with anhydrous magnesium sulfate (MgSO.sub.4), filtrated, and concented under reduced pressure. The concentrated residue was purified by a silica gel column chromatography, to obtain the title compound (1.6 g, yield 51%).

(392) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.031.25 (m, 3H), 2.76 (s, 3H), 3.34 (s, 1H), 4.80 (br s 1H), 5.04 (t, J=12.5 Hz, 1H), 5.14 (s, 1H), 7.207.53 (m, 4H)

Example 16

Synthesis of 1-(2-chlorophenyl)-(S)-1-hydroxypropyl-(S)-2-N-propylcarbamate (16)

(393) ##STR00141##

(394) The substantially same method as described in Example 15 was conducted, except that propylamine was used instead of methylamine solution (CH.sub.3NH.sub.2 in EtOH), to obtain the title compound (0.79 g, yield 25%).

(395) .sup.1H NMR (400 MHz, CDCl.sub.3) 0.90 (t, J=6.8 Hz, 3H), 1.20 (d, J=5.96 Hz, 3H), 1.49 (dd, J=14.2 Hz, 2H), 3.11 (d, J=6.28 Hz, 2H), 3.34 (s, 1H), 4.84 (br s, 1H), 5.05 (t, J=5.88 Hz, 1H), 5.14 (s, 1H), 7.227.53 (m, 4H)

Example 17

Synthesis of 1-(2-chlorophenyl)-(S)-1-hydroxypropyl-(R)-2-N-isopropylcarbamate (17)

(396) ##STR00142##

(397) The substantially same method as described in Example 15 was conducted, except that isopropylamine was used instead of methylamine solution (CH.sub.3NH.sub.2 in EtOH), to obtain the title compound (1.5 g, yield 41%).

(398) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.14 (dd, J=6.5 Hz, 6H), 1.19 (d, J=6.4 Hz, 3H), 3.21 (s, 1H), 3.733.82 (m, 1H), 4.59 (br s, 1H), 5.015.07 (m, 1H), 5.14 (t, J=5.8 Hz, 1H), 7.207.53 (m, 4H)

Example 18

Synthesis of 1-(2-chlorophenyl)-(S)-1-hydroxypropyl-(R)-2-N-cyclopropylcarbamate (18)

(399) ##STR00143##

(400) The substantially same method as described in Example 15 was conducted, except that cyclopropylamine was used instead of methylamine solution (CH.sub.3NH.sub.2 in EtOH), to obtain the title compound (2.2 g, yield 43%).

(401) .sup.1H NMR (400 MHz, CDCl.sub.3) 0.500.56 (m, 2H), 0.74 (d, J=7.21 Hz, 2H), 1.25 (s, 3H), 2.562.61 (m, 1H), 3.72 (s, 1H), 4.98 (br s, 1H), 5.055.11 (m, 1H), 7.16 (s, 1H), 7.237.54 (m, 4H)

Example 19

Synthesis of 1-(2-chlorophenyl)-(S)-1-hydroxypropyl-(R)-2-N-cyclohexyl carbamate (19)

(402) ##STR00144##

(403) The substantially same method as described in Example 15 was conducted, except that cyclohexylamine was used instead of methylamine solution (CH.sub.3NH.sub.2 in EtOH), to obtain the title compound (1.1 g, yield 26%).

(404) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.061.40 (m, 7H), 1.561.61 (m, 2H), 1.691.71 (m, 2H), 1.871.94 (m, 2H), 3.19 (d, J=4.32 Hz, 1H), 3.45 (s, 1H), 4.64 (br s 1H), 5.025.07 (m, 1H), 5.14 (t, J=6.08 Hz, 1H) 7.207.53 (m, 4H)

Example 20

Synthesis of 1-(2-chlorophenyl)-(S)-1-hydroxypropyl-(S)-2-N-benzyl carbamate (20)

(405) ##STR00145##

(406) The substantially same method as described in Example 15 was conducted, except that benzylamine was used instead of methylamine solution (CH.sub.3NH.sub.2 in EtOH), to obtain the title compound (1.2 g, yield 18%).

(407) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.27 (d, J=10 Hz, 3H), 3.12 (d, J=5 Hz, 1H), 4.37 (d, J=6 Hz, 2H), 5.125.19 (m, 3H), 7.157.56 (m, 9H)

Example 21

Synthesis of 1-(2-chlorophenyl)-(S)-1-hydroxypropyl-(S)-2-N-bicyclo[2,2,1]heptanescarbamate (21)

(408) ##STR00146##

(409) The substantially same method as described in Example 15 was conducted, except that 2-aminonorbornane was used instead of methylamine solution (CH.sub.3NH.sub.2 in EtOH), to obtain the title compound (1.7 g, yield 32%).

(410) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.081.35 (m, 9H), 1.65 (br s, 1H), 1.751.71 (m, 1H), 2.142.24 (m, 1H), 2.272.30 (m, 1H), 3.233.29 (m, 1H), 3.473.52 (m, 1H), 4.67 (br s, 1H), 5.015.09 (m, 1H), 5.125.18 (m, 1H), 7.227.55 (m, 4H)

Example 22

Synthesis of 1-(2-chlorophenyl)-(R)-1-hydroxypropyl-(R)-2-N-methylcarbamate (22)

(411) ##STR00147##

(412) The substantially same method as described in Example 15 was conducted, except that 1-(2-chlorophenyl)-(R,R)-1,2-propanediol (Preparation example 15) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-propanediol (Preparation example 14), to obtain the title compound (3.36 g, yield 60%).

(413) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.20 (d, J=6.8 Hz, 3H), 2.80 (d, J=4.8 Hz, 3H), 3.20 (d, J=4.4 Hz, 1H), 4.75 (br s, 1H), 5.035.09 (m, 1H), 5.145.17 (m, 1H), 7.227.55 (m, 4H)

Example 23

Synthesis of 1-(2-chlorophenyl)-(R)-1-hydroxypropyl-(R)-2-N-propylcarbamate (23)

(414) ##STR00148##

(415) The substantially same method as described in Example 22 was conducted, except that propylamine was used instead of methylamine solution (CH.sub.3NH.sub.2 in EtOH), to obtain the title compound (3.1 g, yield 53%).

(416) .sup.1H NMR (400 MHz, CDCl.sub.3) 0.92 (t, J=7.6 Hz, 3H), 1.21 (d, J=6.4 Hz, 3H), 1.51 (m, 2H), 3.093.14 (m, 2H), 3.28 (d, J=4.4 Hz, 1H), 4.82 (br s, 1H), 5.035.09 (m, 1H), 5.145.17 (m, 1H), 7.227.55 (m. 4H)

Example 24

Synthesis of 1-(2-chlorophenyl)-(R)-1-hydroxypropyl-(R)-2-N-isopropylcarbamate (24)

(417) ##STR00149##

(418) The substantially same method as described in Example 22 was conducted, except that isopropylamine was used instead of methylamine solution (CH.sub.3NH.sub.2 in EtOH), to obtain the title compound (0.16 g, yield 27%).

(419) .sup.1H NMR (400 MHz, CDCl.sub.3) 0.881.16 (m, 6H), 1.191.26 (m, 3H), 3.34 (s, 1H), 3.713.78 (m, 1H), 4.62 (br s, 1H), 5.03 (t, J=5.8 Hz, 1H), 5.13 (d, J=4.9 Hz, 1H), 7.207.53 (m, 4H)

Example 25

Synthesis of 1-(2-chlorophenyl)-(R)-1-hydroxypropyl-(R)-2-N-cyclopropylcarbamate (25)

(420) ##STR00150##

(421) The substantially same method as described in Example 22 was conducted, except that cyclopropylamine was used instead of methylamine solution (CH.sub.3NH.sub.2 in EtOH), to obtain the title compound (3.7 g, yield 60%).

(422) .sup.1H NMR (400 MHz, CDCl.sub.3) 0.490.54 (m, 2H), 0.74 (d, J=7.2 Hz, 2H), 1.22 (s, 3H), 2.552.60 (m, 1H), 3.16 (s, 1H), 5.00 (s, 1H), 5.045.11 (m, 1H), 5.16 (s, 1H), 7.237.54 (m, 4H)

Example 26

Synthesis of 1-(2-chlorophenyl)-(R)-1-hydroxypropyl-(R)-2-N-cyclohexyl carbamate (26)

(423) ##STR00151##

(424) The substantially same method as described in Example 22 was conducted, except that cyclohexylamine was used instead of methylamine solution (CH.sub.3NH.sub.2 in EtOH), to obtain the title compound (1.9 g, yield 28%).

(425) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.051.38 (m, 8H), 1.581.70 (m, 3H), 1.851.95 (m, 2H), 3.393.47 (m, 1H), 3.56 (s, 1H), 4.79 (br s, 1H), 5.015.07 (m, 1H), 5.14 (t, J=5.2 Hz, 1H), 7.207.54 (m, 4H)

Example 27

Synthesis of 1-(2-chlorophenyl)-(R)-1-hydroxypropyl-(R)-2-N-benzylcarbamate (27)

(426) ##STR00152##

(427) The substantially same method as described in Example 22 was conducted, except that benzylamine was used instead of methylamine solution (CH.sub.3NH.sub.2 in EtOH), to obtain the title compound (0.52 g, yield 19%).

(428) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.25 (d, J=6 Hz, 3H), 1.64 (s, 1H), 3.13 (d, J=4.4 Hz, 1H), 4.37 (d, J=5.6 Hz, 2H), 5.125.19 (m, 2H), 7.237.55 (m, 9H)

Example 28

Synthesis of 1-(2-chlorophenyl)-(R)-1-hydroxypropyl-(R)-2-N-bicyclo[2,2,1]heptanecarbamate (28)

(429) ##STR00153##

(430) The substantially same method as described in Example 22 was conducted, except that 2-aminonorbornane was used instead of methylamine solution (CH.sub.3NH.sub.2 in EtOH), to obtain the title compound (1.7 g, yield 2050%).

(431) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.081.35 (m, 9H), 1.65 (br s, 1H), 1.751.71 (m, 1H), 2.142.24 (m, 1H), 2.272.30 (m, 1H), 3.233.29 (m, 1H), 3.473.52 (m, 1H), 4.67 (br s, 1H), 5.015.09 (m, 1H), 5.125.18 (m, 1H), 7.227.55 (m, 4H)

Example 29

Synthesis of 1-(2-chlorophenyl)-1-hydroxypropyl-2-N-methylcarbamate (29)

(432) ##STR00154##

(433) The substantially same method as described in Example 15 was conducted, except that 1-(2-chlorophenyl)-1,2-propanediol (Preparation example 16) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-propanediol (Preparation example 14), to obtain the title compound (2.6 g, yield 45%).

(434) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.21 (d, J=6 Hz, 3H), 2.81 (d, J=5 Hz, 3H), 3.14 (d, J=4 Hz, 1H), 4.72 (br s, 1H), 5.07 (dd, J=6 Hz, 1H), 5.16 (t, J=6 Hz, 1H), 7.227.56 (m, 4H)

Example 30

Synthesis of 1-(2-chlorophenyl)-1-hydroxypropyl-2-N-propylcarbamate (30)

(435) ##STR00155##

(436) The substantially same method as described in Example 29 was conducted, except that propylamine was used instead of methylamine solution (CH.sub.3NH.sub.2 in EtOH), to obtain the title compound (1.0 g, yield 17%).

(437) .sup.1H NMR (400 MHz, CDCl.sub.3) 0.92 (t, J=7 Hz, 3H), 1.21 (d, J=6 Hz, 3H), 1.53 (dd, J=7 Hz, 2H), 3.13 (dd, J=7 Hz, 2H), 3.28 (d, 1H), 4.82 (S, 1H), 5.06 (dd, J=7 Hz, 1H), 5.16 (t, J=5 Hz, 1H), 7.217.56 (m, 4H)

Example 31

Synthesis of 1-(2-chlorophenyl)-1-hydroxypropyl-2-N-isopropylcarbamate (31)

(438) ##STR00156##

(439) The substantially same method as described in Example 29 was conducted, except that isopropylamine was used instead of methylamine solution (CH.sub.3NH.sub.2 in EtOH), to obtain the title compound (0.54 g, yield 16%).

(440) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.16 (dd, J=6 Hz, 6H), 1.21 (d, J=6 Hz, 3H), 3.23 (d, J=6 Hz, 1H), 3.753.84 (m, 1H), 4.61 (br s, 1H), 5.06 (t, J=6 Hz, 1H), 5.16 (t, J=6 Hz, 1H), 7.227.56 (m, 4H)

Example 32

Synthesis of 1-(2-chlorophenyl)-1-hydroxypropyl-2-N-cyclopropylcarbamate (32)

(441) ##STR00157##

(442) The substantially same method as described in Example 29 was conducted, except that cyclopropylamine was used instead of methylamine solution (CH.sub.3NH.sub.2 in EtOH), to obtain the title compound (1.0 g, yield 17%).

(443) .sup.1H NMR (400 MHz, CDCl.sub.3) 0.50 (t, J=6 Hz, 2H), 0.77 (t, J=3 Hz, 2H), 1.12 (d, J=7 Hz, 3H), 2.532.59 (m, 1H), 3.22 (d, J=4 Hz, 1H), 5.08 (dd, J=6 Hz, 1H), 5.15 (S, 1H), 7.227.55 (m, 4H)

Example 33

Synthesis of 1-(2-chlorophenyl)-1-hydroxypropyl-2-N-cyclohexylcarbamate (33)

(444) ##STR00158##

(445) The substantially same method as described in Example 29 was conducted, except that cyclohexylamine was used instead of methylamine solution (CH.sub.3NH.sub.2 in EtOH), to obtain the title compound (2.2 g, yield 33%).

(446) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.071.17 (m, 3H), 1.21 (d, J=6 Hz, 3H), 1.291.42 (m, 3H), 1.72 (dd, J=6 Hz, 2H), 1.92 (dd, J=6 Hz, 2H), 3.26 (d, J=4 Hz, 1H), 3.46 (t, J=4 Hz, 1H), 4.68 (d, J=6 Hz, 1H), 5.07 (dd, J=6 Hz, 1H), 5.16 (t, J=6 Hz, 1H), 7.227.55 (m, 4H)

Example 34

Synthesis of 1-(2-chlorophenyl)-1-hydroxypropyl-2-N-benzylcarbamate (34)

(447) ##STR00159##

(448) The substantially same method as described in Example 29 was conducted, except that benzylamine was used instead of methylamine solution (CH.sub.3NH.sub.2 in EtOH), to obtain the title compound (1.3 g, yield 19%).

(449) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.25 (d, J=6 Hz, 3H), 3.16 (d, J=4 Hz, 1H), 4.36 (d, J=6 Hz, 2H), 5.14 (dd, J=6 Hz, 3H), 7.237.56 (m, 9H), yield: 19% (1.3 g)

Example 35

Synthesis of 1-(2-chlorophenyl)-1-hydroxypropyl-2-N-bicyclo[2,2,1]heptanecarbamate (35)

(450) ##STR00160##

(451) The substantially same method as described in Example 29 was conducted, except that 2-aminonorbornane was used instead of methylamine solution (CH.sub.3NH.sub.2 in EtOH), to obtain the title compound (1.7 g, yield 2050%).

(452) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.081.35 (m, 9H), 1.65 (br s, 1H), 1.751.71 (m, 1H), 2.142.24 (m, 1H), 2.272.30 (m, 1H), 3.233.29 (m, 1H), 3.473.52 (m, 1H), 4.67 (br s, 1H), 5.015.09 (m, 1H), 5.125.18 (m, 1H), 7.227.55 (m, 4H)

Example 36

Synthesis of 1-(2,4-dichlorophenyl)-(S)-1-hydroxypropyl-(S)-2-carbamate (36)

(453) ##STR00161##

(454) The substantially same method as described in Example 1 was conducted, except that 1-(2,4-dichlorophenyl)-(S,S)-1,2-(Bis-trimethylsilanyloxy)propane (Preparation Example 83) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-(Bis-trimethylsilanyloxy) propane (Preparation example 69) to obtain the title compound (1.8 g, yield 6090%).

(455) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.22 (d, J=6.4 Hz, 3H), 4.16 (br t, 1H) 4.96 (br t, 3H), 5.07 (t, J=4.8 Hz, 1H), 7.237.52 (m, 3H)

Example 37

Synthesis of 1-(2,6-dichlorophenyl)-(S)-1-hydroxypropyl-(S)-2-carbamate (37)

(456) ##STR00162##

(457) The substantially same method as described in Example 1 was conducted, except that 1-(2,6-dichlorophenyl)-(S,S)-1,2-(Bis-trimethylsilanyloxy)propane (Preparation Example 84) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-(Bis-trimethylsilanyloxy) propane (Preparation example 69) to obtain the title compound (2.6 g, yield 6090%)

Example 38

Synthesis of 1-(2,3-dichlorophenyl)-(S)-1-hydroxypropyl-(S)-2-carbamate (38)

(458) ##STR00163##

(459) The substantially same method as described in Example 1 was conducted, except that 1-(2,3-dichlorophenyl)-(S,S)-1,2-(Bis-trimethylsilanyloxy)propane (Preparation Example 85) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-(Bis-trimethylsilanyloxy) propane (Preparation example 69) to obtain the title compound (1.4 g, yield 6090%)

(460) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.15 (d, J=6.4 Hz, 3H), 3.66 (d, J=9.2 Hz, 1H), 4.73 (br s, 2H), 5.43 (t, J=9.0 Hz, 1H), 5.625.69 (m, 1H), 7.187.22 (m, 3H),

Example 39

Synthesis of 1-(2,4-dichlorophenyl)-(S)-1-hydroxybutyl-(S)-2-carbamate (39)

(461) ##STR00164##

(462) The substantially same method as described in Example 1 was conducted, except that 1-(2,4-dichlorophenyl)-(S,S)-1,2-(Bis-trimethylsilanyloxy)butane (Preparation Example 86) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-(Bis-trimethylsilanyloxy) propane (Preparation example 69) to obtain the title compound (2.3 g, yield 6090%).

(463) .sup.1H NMR (400 MHz, CDCl.sub.3) 0.96 (t, J=7.4 Hz, 3H), 1.581.74 (m, 2H), 2.98 (d, J=5.6 Hz, 1H) 4.68 (br s, 2H), 5.59 (dt, J=5.2, 8.8 Hz, 1H), 5.19 (t, J=5.4 Hz, 1H), 7.307.50 (m, 3H)

Example 40

Synthesis of 1-(2,6-dichlorophenyl)-(S)-1-hydroxybutyl-(S)-2-carbamate (40)

(464) ##STR00165##

(465) The substantially same method as described in Example 1 was conducted, except that 1-(2,6-dichlorophenyl)-(S,S)-1,2-(Bis-trimethylsilanyloxy)butane (Preparation Example 87) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-(Bis-trimethylsilanyloxy) propane (Preparation example 69) to obtain the title compound (1.7 g, yield 6090%).

(466) .sup.1H NMR (400 MHz, CDCl.sub.3) 0.92 (t, J=7.4 Hz, 3H), 1.301.38 (m, 1H), 1.571.64 (m, 1H), 3.74 (d, J=9.2 Hz, 1H), 4.80 (br s, 2H), 5.405.50 (m, 2H), 7.177.34 (m, 3H)

Example 41

Synthesis of 1-(2,4-dichlorophenyl)-(S)-1-hydroxy-3-methyl-butyl-(S)-2-carbamate (41)

(467) ##STR00166##

(468) The substantially same method as described in Example 1 was conducted, except that 1-(2,4-dichlorophenyl)-3-methyl-(S,S)-1,2-(Bis-trimethylsilanyloxy)butane (Preparation Example 88) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-(Bis-trimethylsilanyloxy) propane (Preparation example 69) to obtain the title compound (1.9 g, yield 6090%).

(469) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.00 (1, J=7.2 Hz, 6H), 1.731.79 (m, 1H), 3.673.69 (m, 1H), 4.85 (br s, 2H), 5.405.43 (m, 1H), 5.495.54 (m, 1H), 7.307.50 (m, 3H)

Example 42

Synthesis of 1-(2,6-dichlorophenyl)-(S)-1-hydroxy-3-methyl-butyl-(S)-2-carbamate (42)

(470) ##STR00167##

(471) The substantially same method as described in Example 1 was conducted, except that 1-(2,6-dichlorophenyl)-3-methyl-(S,S)-1,2-(Bis-trimethylsilanyloxy)butane (Preparation Example 89) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-(Bis-trimethylsilanyloxy) propane (Preparation example 69) to obtain the title compound (2.4 g, yield 6090%).

(472) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.00 (t, J=7.2 Hz, 6H), 1.731.79 (m, 1H), 3.673.69 (m, 1H), 4.85 (br s, 2H), 5.405.43 (m, 1H), 5.495.54 (m, 1H), 7.167.33 (m, 3H)

Example 43

Synthesis of 1-(2,4-dichlorophenyl)-(S)-1-hydroxyhexyl-(S)-2-carbamate (43)

(473) ##STR00168##

(474) The substantially same method as described in Example 1 was conducted, except that 1-(2,4-dichlorophenyl)-(S,S)-1,2-(Bis-trimethylsilanyloxy)hexane (Preparation Example 90) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-(Bis-trimethylsilanyloxy) propane (Preparation example 69) to obtain the title compound (2.2 g, yield 6090%).

(475) .sup.1H NMR (400 MHz, CDCl.sub.3) 0.89 (t, J=3.6 Hz, 3H), 1.281.42 (m, 4H), 1.521.59 (m, 1H), 1.641.71 (m, 1H), 2.98 (d, J=5.6 Hz, 1H), 4.67 (br s, 2H), 4.965.00 (m, 1H), 5.17 (t, J=5.6 Hz, 1H), 7.307.49 (m 3H)

Example 44

Synthesis of 1-(2,6-dichlorophenyl)-(S)-1-hydroxyhexyl-(S)-2-carbamate (44)

(476) ##STR00169##

(477) The substantially same method as described in Example 1 was conducted, except that 1-(2,6-dichlorophenyl)-(S,S)-1,2-(Bis-trimethylsilanyloxy)hexane (Preparation Example 91) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-(Bis-trimethylsilanyloxy) propane (Preparation example 69) to obtain the title compound (2.1 g, yield 6090%)

(478) .sup.1H NMR (400 MHz, CDCl.sub.3) 0.84 (t, J=7.0 Hz, 3H), 1.201.35 (m, 4H), 1.361.41 (m, 1H), 1.591.63 (m, 1H), 3.71 (d, J=10.0 Hz, 1H), 4.74 (br s, 2H), 5.405.44 (m, 1H), 5.525.57 (m, 1H), 7.177.35 (m, 3H)

Example 45

Synthesis of 1-(2,4-dichlorophenyl)-(R)-1-hydroxypropyl-(R)-2-carbamate (45)

(479) ##STR00170##

(480) The substantially same method as described in Example 1 was conducted, except that 1-(2,4-dichlorophenyl)-(R,R)-1,2-(Bis-trimethylsilanyloxy)propane (Preparation Example 92) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-(Bis-trimethylsilanyloxy) propane (Preparation example 69) to obtain the title compound (1.2 g, yield 6090%),

(481) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.22 (d, J=6.4 Hz, 3H), 4.16 (br t, 1H) 4.96 (br t, 3H), 5.07 (t, J=4.8 Hz, 1H), 7.237.52 (m, 3H)

Example 46

Synthesis of 1-(2,6-dichlorophenyl)-(R)-1-hydroxypropyl-(R)-2-carbamate (46)

(482) ##STR00171##

(483) The substantially same method as described in Example 1 was conducted, except that 1-(2,6-dichlorophenyl)-(R,R)-1,2-(Bis-trimethylsilanyloxy)propane (Preparation Example 93) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-(Bis-trimethylsilanyloxy) propane (Preparation example 69) to obtain the title compound (1.7 g, yield 6090%),

(484) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.15 (d, J=6.4 Hz, 3H), 3.66 (d, J=9.2 Hz, 1H), 4.73 (br s, 2H), 5.43 (t, J=9.0 Hz, 1H), 5.625.69 (m, 1H), 7.187.22 (m, 3H),

Example 47

Synthesis of 1-(2,3-dichlorophenyl)-(R)-1-hydroxypropyl-(R)-2-carbamate (47)

(485) ##STR00172##

(486) The substantially same method as described in Example 1 was conducted, except that 1-(2,3-dichlorophenyl)-(R,R)-1,2-(Bis-trimethylsilanyloxy)propane (Preparation Example 94) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-(Bis-trimethylsilanyloxy) propane (Preparation example 69) to obtain the title compound (2.0 g, yield 6090%)

(487) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.15 (d, J=6.4 Hz, 3H), 3.66 (d, J=9.2 Hz, 1H), 4.73 (br s, 2H), 5.43 (t, J=9.0 Hz, 1H), 5.625.69 (m, 1H), 7.187.22 (m, 3H),

Example 48

Synthesis of 1-(2,4-dichlorophenyl)-(R)-1-hydroxybutyl-(R)-2-carbamate (48)

(488) ##STR00173##

(489) The substantially same method as described in Example 1 was conducted, except that 1-(2,4-dichlorophenyl)-(R,R)-1,2-(Bis-trimethylsilanyloxy)butane (Preparation Example 95) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-(Bis-trimethylsilanyloxy) propane (Preparation example 69) to obtain the title compound (2.3 g, yield 6090%).

(490) .sup.1H NMR (400 MHz, CDCl.sub.3) 0.96 (t, J=7.4 Hz, 3H), 1.581.74 (m, 2H), 2.98 (d, J=5.6 Hz, 1H) 4.68 (br s, 2H), 5.59 (dt, J=5.2, 8.8 Hz, 1H), 5.19 (t, J=5.4 Hz, 1H), 7.307.50 (m, 3H)

Example 49

Synthesis of 1-(2,6-dichlorophenyl)-(R)-1-hydroxybutyl-(R)-2-carbamate (49)

(491) ##STR00174##

(492) The substantially same method as described in Example 1 was conducted, except that 1-(2,6-dichlorophenyl)-(R,R)-1,2-(Bis-trimethylsilanyloxy)butane (Preparation Example 96) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-(Bis-trimethylsilanyloxy) propane (Preparation example 69) to obtain the title compound (2.5 g, yield 6090%).

(493) .sup.1H NMR (400 MHz, CDCl.sub.3) 0.92 (t, J=7.4 Hz, 3H), 1.301.38 (m, 1H), 1.571.64 (m, 1H), 3.74 (d, J=9.2 Hz, 1H), 4.80 (br s, 2H), 5.405.50 (m, 2H), 7.177.34 (m, 3H)

Example 50

Synthesis of 1-(2,4-dichlorophenyl)-(R)-1-hydroxy-3-methyl-butyl-(R)-2-carbamate (50)

(494) ##STR00175##

(495) The substantially same method as described in Example 1 was conducted, except that 1-(2,4-dichlorophenyl)-3-methyl-(R,R)-1,2-(Bis-trimethylsilanyloxy)butane (Preparation Example 97) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-(Bis-trimethylsilanyloxy) propane (Preparation example 69) to obtain the title compound (2.8 g, yield 6090%).

(496) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.00 (1, J=7.2 Hz, 6H), 1.731.79 (m, 1H), 3.673.69 (m, 1H), 4.85 (br s, 2H), 5.405.43 (m, 1H), 5.495.54 (m, 1H), 7.307.50 (m, 3H)

Example 51

Synthesis of 1-(2,6-dichlorophenyl)-(R)-1-hydroxy-3-methyl-butyl-(R)-2-carbamate (51)

(497) ##STR00176##

(498) The substantially same method as described in Example 1 was conducted, except that 1-(2,6-dichlorophenyl)-3-methyl-(R,R)-1,2-(Bis-trimethylsilanyloxy)butane (Preparation Example 98) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-(Bis-trimethylsilanyloxy) propane (Preparation example 69) to obtain the title compound (2.6 g, yield 6090%).

(499) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.00 (1, J=7.2 Hz, 6H), 1.731.79 (m, 1H), 3.673.69 (m, 1H), 4.85 (br s, 2H), 5.405.43 (m, 1H), 5.495.54 (m, 1H), 7.167.33 (m, 3H)

Example 52

Synthesis of 1-(2,4-dichlorophenyl)-(R)-1-hydroxyhexyl-(R)-2-carbamate (52)

(500) ##STR00177##

(501) The substantially same method as described in Example 1 was conducted, except that 1-(2,4-dichlorophenyl)-(R,R)-1,2-(Bis-trimethylsilanyloxy)hexane (Preparation Example 99) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-(Bis-trimethylsilanyloxy) propane (Preparation example 69) to obtain the title compound (2.5 g, yield 6090%).

(502) .sup.1H NMR (400 MHz, CDCl.sub.3) 0.89 (t, J=3.6 Hz, 3H), 1.281.42 (m, 4H), 1.521.59 (m, 1H), 1.641.71 (m, 1H), 2.98 (d, J=5.6 Hz, 1H), 4.67 (br s, 2H), 4.965.00 (m, 1H), 5.17 (t, J=5.6 Hz, 1H), 7.307.49 (m, 3H)

Example 53

Synthesis of 1-(2,6-dichlorophenyl)-(R)-1-hydroxyhexyl-(R)-2-carbamate (53)

(503) ##STR00178##

(504) The substantially same method as described in Example 1 was conducted, except that 1-(2,6-dichlorophenyl)-(R,R)-1,2-(Bis-trimethylsilanyloxy)hexane (Preparation Example 100) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-(Bis-trimethylsilanyloxy) propane (Preparation example 69) to obtain the title compound (2.4 g, yield 6090%).

(505) .sup.1H NMR (400 MHz, CDCl.sub.3) 0.84 (t, J=7.0 Hz, 3H), 1.201.35 (m, 4H), 1.361.41 (m, 1H), 1.591.63 (m, 1H), 3.71 (d, J=10.0 Hz, 1H), 4.74 (br s, 2H), 5.405.44 (m, 1H), 5.525.57 (m, 1H), 7.177.35 (m, 3H)

Example 54

Synthesis of 1-(2,4-dichlorophenyl)-1-hydroxypropyl-2-carbamate (54)

(506) ##STR00179##

(507) The substantially same method as described in Example 1 was conducted, except that 1-(2,4-dichlorophenyl)-1,2-(Bis-trimethylsilanyloxy)propane (Preparation Example 101) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-(Bis-trimethylsilanyloxy) propane (Preparation example 69) to obtain the title compound (1.7 g, yield 6090%).

(508) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.22 (d, J=6.4 Hz, 3H), 4.16 (br t, 1H) 4.96 (br t, 3H), 5.07 (t, J=4.8 Hz, 1H), 7.237.52 (m, 3H)

Example 55

Synthesis of 1-(2,6-dichlorophenyl)-1-hydroxypropyl-2-carbamate (55)

(509) ##STR00180##

(510) The substantially same method as described in Example 1 was conducted, except that 1-(2,6-dichlorophenyl)-1,2-(Bis-trimethylsilanyloxy)propane (Preparation Example 102) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-(Bis-trimethylsilanyloxy) propane (Preparation example 69) to obtain the title compound (2.4 g, yield 6090%).

(511) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.15 (d, J=6.4 Hz, 3H), 3.66 (d, J=9.2 Hz, 1H), 4.73 (br s, 2H), 5.43 (t, J=9.0 Hz, 1H), 5.625.69 (m, 1H), 7.187.22 (m, 3H),

Example 56

Synthesis of 1-(2,3-dichlorophenyl)-1-hydroxypropyl-2-carbamate (56)

(512) ##STR00181##

(513) The substantially same method as described in Example 1 was conducted, except that 1-(2,3-dichlorophenyl)-1,2-(Bis-trimethylsilanyloxy)propane (Preparation Example 103) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-(Bis-trimethylsilanyloxy) propane (Preparation example 69) to obtain the title compound (1.6 g, yield 6090%).

(514) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.15 (d, J=6.4 Hz, 3H), 3.66 (d, J=9.2 Hz, 1H), 4.73 (br s, 2H), 5.43 (t, J=9.0 Hz, 1H), 5.625.69 (m, 1H), 7.187.22 (m, 3H),

Example 57

Synthesis of 1-(2,4-dichlorophenyl)-1-hydroxybutyl-2-carbamate (57)

(515) ##STR00182##

(516) The substantially same method as described in Example 1 was conducted, except that 1-(2,4-dichlorophenyl)-1,2-(Bis-trimethylsilanyloxy)butane (Preparation Example 104) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-(Bis-trimethylsilanyloxy) propane (Preparation example 69) to obtain the title compound (1.7 g, yield 6090%).

(517) .sup.1H NMR (400 MHz, CDCl.sub.3) 0.96 (t, J=7.4 Hz, 3H), 1.581.74 (m, 2H), 2.98 (d, J=5.6 Hz, 1H) 4.68 (br s, 2H), 5.59 (dt, J=5.2, 8.8 Hz, 1H), 5.19 (t, J=5.4 Hz, 1H), 7.307.50 (m, 3H)

Example 58

Synthesis of 1-(2,6-dichlorophenyl)-1-hydroxybutyl-2-carbamate (58)

(518) ##STR00183##

(519) The substantially same method as described in Example 1 was conducted, except that 1-(2,6-dichlorophenyl)-1,2-(Bis-trimethylsilanyloxy)butane (Preparation Example 105) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-(Bis-trimethylsilanyloxy) propane (Preparation example 69) to obtain the title compound (2.4 g, yield 6090%).

(520) .sup.1H NMR (400 MHz, CDCl.sub.3) 0.92 (t, J=7.4 Hz, 3H), 1.301.38 (m, 1H), 1.571.64 (m, 1H), 3.74 (d, J=9.2 Hz, 1H), 4.80 (br s, 2H), 5.405.50 (m, 2H), 7.177.34 (m, 3H)

Example 59

Synthesis of 1-(2,4-dichlorophenyl)-1-hydroxy-3-methyl-butyl-2-carbamate (59)

(521) ##STR00184##

(522) The substantially same method as described in Example 1 was conducted, except that 1-(2,4-dichlorophenyl)-3-methyl-1,2-(Bis-trimethylsilanyloxy)butane (Preparation Example 106) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-(Bis-trimethylsilanyloxy) propane (Preparation example 69) to obtain the title compound (1.9 g, yield 6090%).

(523) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.00 (t, J=7.2 Hz, 6H), 1.731.79 (m, 1H), 3.673.69 (m, 1H), 4.85 (br s, 2H), 5.405.43 (m, 1H), 5.495.54 (m, 1H), 7.307.50 (m, 3H)

Example 60

Synthesis of 1-(2,6-dichlorophenyl)-1-hydroxy-3-methyl-butyl-2-carbamate (60)

(524) ##STR00185##

(525) The substantially same method as described in Example 1 was conducted, except that 1-(2,6-dichlorophenyl)-3-methyl-1,2-(Bis-trimethylsilanyloxy)butane (Preparation Example 107) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-(Bis-trimethylsilanyloxy) propane (Preparation example 69) to obtain the title compound (1.7 g, yield 6090%).

(526) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.00 (t, J=7.2 Hz, 6H), 1.731.79 (m, 1H), 3.673.69 (m, 1H), 4.85 (br s, 2H), 5.405.43 (m, 1H), 5.495.54 (m, 1H), 7.167.33 (m, 3H)

Example 61

Synthesis of 1-(2,4-dichlorophenyl)-1-hydroxyhexyl-2-carbamate (61)

(527) ##STR00186##

(528) The substantially same method as described in Example 1 was conducted, except that 1-(2,4-dichlorophenyl)-1,2-(Bis-trimethylsilanyloxy)hexane (Preparation Example 108) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-(Bis-trimethylsilanyloxy) propane (Preparation example 69) to obtain the title compound (2.6 g, yield 6090%).

(529) .sup.1H NMR (400 MHz, CDCl.sub.3) 0.89 (t, J=3.6 Hz, 3H), 1.281.42 (m, 4H), 1.521.59 (m, 1H), 1.641.71 (m, 1H), 2.98 (d, J=5.6 Hz, 1H), 4.67 (br s, 2H), 4.965.00 (m, 1H), 5.17 (t, J=5.6 Hz, 1H), 7.307.49 (m, 3H)

Example 62

Synthesis of 1-(2,6-dichlorophenyl)-1-hydroxyhexyl-2-carbamate (62)

(530) ##STR00187##

(531) The substantially same method as described in Example 1 was conducted, except that 1-(2,6-dichlorophenyl)-1,2-(Bis-trimethylsilanyloxy)hexane (Preparation Example 109) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-(Bis-trimethylsilanyloxy) propane (Preparation example 69) to obtain the title compound (2.5 g, yield 6090%).

(532) .sup.1H NMR (400 MHz, CDCl.sub.3) 0.84 (t, J=7.0 Hz, 3H), 1.201.35 (m, 4H), 1.361.41 (m, 1H), 1.591.63 (m, 1H), 3.71 (d, J=10.0 Hz, 1H), 4.74 (br s, 2H), 5.405.44 (m, 1H), 5.525.57 (m, 1H), 7.177.35 (m, 3H)

Example 63

Synthesis of 1-(2-fluorophenyl)-(S)-1-hydroxypropyl-(S)-2-carbamate (63)

(533) ##STR00188##

(534) The substantially same method as described in Example 1 was conducted, except that 1-(2-fluorophenyl)-(S,S)-1,2-(Bis-trimethylsilanyloxy)propane (Preparation Example 110) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-(Bis-trimethylsilanyloxy) propane (Preparation example 69) to obtain the title compound (1.8 g, yield 6090%).

(535) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.19 (d, J=5.2 Hz, 3H), 2.93 (d, J=4.4 Hz, 1H), 4.71 (br s, 2H), 4.995.06 (m, H), 7.047.48 (m, 4H)

Example 64

Synthesis of 1-(2-fluorophenyl)-(R)-1-hydroxypropyl-(R)-2-carbamate (64)

(536) ##STR00189##

(537) The substantially same method as described in Example 1 was conducted, except that 1-(2-fluorophenyl)-(R,R)-1,2-(Bis-trimethylsilanyloxy)propane (Preparation Example 111) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-(Bis-trimethylsilanyloxy) propane (Preparation example 69) to obtain the title compound (1.6 g, yield 6090%).

(538) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.19 (d, J=5.2 Hz, 3H), 2.93 (d, J=4.4 Hz, 1H), 4.71 (br s, 2H), 4.995.06 (m, H), 7.047.48 (m, 4H)

Example 65

Synthesis of 1-(2-iodophenyl)-(S)-1-hydroxypropyl-(S)-2-carbamate (65)

(539) ##STR00190##

(540) The substantially same method as described in Example 1 was conducted, except that 1-(2-iodophenyl)-(S,S)-1,2-(Bis-trimethylsilanyloxy)propane (Preparation Example 112) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-(Bis-trimethylsilanyloxy) propane (Preparation example 69) to obtain the title compound (2.2 g, yield 6090%).

(541) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.27 (d, J=6.4 Hz, 3H), 3.09 (br s, 1H), 4.83 (br s, 2H), 5.005.10 (m, 2H), 7.007.76 (m, 4H)

Example 66

Synthesis of 1-(2-iodophenyl)-(R)-1-hydroxypropyl-(R)-2-carbamate (66)

(542) ##STR00191##

(543) The substantially same method as described in Example 1 was conducted, except that 1-(2-iodophenyl)-(R,R)-1,2-(Bis-trimethylsilanyloxy)propane (Preparation Example 113) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-(Bis-trimethylsilanyloxy) propane (Preparation example 69) to obtain the title compound (1.7 g, yield 6090%).

(544) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.27 (d, J=6.4 Hz, 3H), 2.95 (d, J=3.6 Hz, 1H), 4.73 (br s, 2H), 5.015.11 (m, 2H), 7.017.86 (m, 4H)

Example 67

Synthesis of 1-(2-iodophenyl)-(S)-1-hydroxybutyl-(S)-2-carbamate (67)

(545) ##STR00192##

(546) The substantially same method as described in Example 1 was conducted, except that 1-(2-iodophenyl)-(S,S)-1,2-(Bis-trimethylsilanyloxy)butane (Preparation Example 114) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-(Bis-trimethylsilanyloxy) propane (Preparation example 69) to obtain the title compound (2.1 g, yield 6090%).

(547) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.27 (d, J=6.4 Hz, 3H), 3.09 (br s, 1H), 4.83 (br s, 2H), 5.005.10 (m, 2H), 7.007.76 (m, 4H)

Example 68

Synthesis of 1-(2-chlorophenyl)-(S)-2-hydroxypropyl-(S)-1-carbamate (68)

(548) ##STR00193##

(549) 1-(2-chlorophenyl)-(S,S)-1,2-propanediol (2.33 g, Preparation example 14) obtained in Preparation Example 14, tetrahydrofuran (THF, 12 ml), and carbonyldiimidazole (CDI, 3.04 g) were put into a flask and stirred at the room temperature. After approximately 3 hours, ammonia solution (NH.sub.4OH, 4 ml) was added thereto. When the reaction was completed, the obtained product was washed with 1M HCl solution and ethylacetate (EA). The separated organic layer was dehydrated with anhydrous magnesium sulfate (MgSO.sub.4), filtrated, and concented under reduced pressure. The concentrated residue was purified by a silica gel column chromatography, to obtain the title compound (0.28 g, yield 1030%).

(550) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.24 (d, J=6.8 Hz, 3H), 2.13 (d, J=4.4 Hz, 1H), 4.124.16 (m, 1H), 4.85 (br s, 2H), 5.98 (d, J=5.6 Hz, 1H), 7.247.43 (m, 4H)

Example 69

Synthesis of 1-(2-chlorophenyl)-(R)-2-hydroxypropyl-(R)-1-carbamate (69)

(551) ##STR00194##

(552) The substantially same method as described in Example 68 was conducted, except that 1-(2-chlorophenyl)-(R,R)-1,2-propanediol (Preparation Example 15) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-propanediol (Preparation example 14) to obtain the title compound (0.77 g, yield 16%).

(553) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.24 (d, J=6.4 Hz, 3H), 2.04 (d, J=4.8 Hz, 1H), 4.114.18 (m, 1H), 4.74 (br s, 2H), 6.00 (d, J=5.6 Hz, 1H), 7.247.43 (m, 4H)

Example 70

Synthesis of 1-(2-chlorophenyl)-2-hydroxypropyl-1-carbamate (70)

(554) ##STR00195##

(555) The substantially same method as described in Example 68 was conducted, except that 1-(2-chlorophenyl)-(R,R)-1,2-propanediol (Preparation Example 16) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-propanediol (Preparation example 14) to obtain the title compound (0.16 g, yield 1030%).

(556) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.24 (d, J=6.4 Hz, 3H), 2.04 (d, J=4.8 Hz, 1H), 4.114.18 (m, 1H), 4.74 (br s, 2H), 6.00 (d, J=5.6 Hz, 1H), 7.247.43 (m, 4H)

Example 71

Synthesis of 1-(2-chlorophenyl)-(S)-2-hydroxypropyl-(S)-1-N-methylcarbamate (71)

(557) ##STR00196##

(558) A regioisomer of monocarbamate was separated and purified by conducting the silica gel column chromatography as described in Example 15, to obtain the title compound (0.70 g, yield 1030%).

(559) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.21 (d, J=6.4 Hz, 3H), 2.80 (d, J=4.8 Hz, 3H), 3.12 (s, 1H), 4.094.16 (m, 1H), 4.86 (br s, 1H), 5.99 (d, J=6.0 Hz, 1H), 7.237.40 (m, 4H)

Example 72

Synthesis of 1-(2-chlorophenyl)-(R)-2-hydroxypropyl-(R)-1-N-methylcarbamate (72)

(560) ##STR00197##

(561) A regioisomer of monocarbamate was separated and purified by conducting the silica gel column chromatography as described in Example 22, to obtain the title compound (0.69 g, yield 1030%).

(562) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.21 (d, J=6.4 Hz, 3H), 2.80 (d, J=4.8 Hz, 3H), 3.12 (s, 1H), 4.094.16 (m, 1H), 4.86 (br s, 1H), 5.99 (d, J=6.0 Hz, 1H), 7.237.40 (m, 4H)

Example 73

Synthesis of 1-(2-chlorophenyl)-2-hydroxypropyl-1-N-methylcarbamate (73)

(563) ##STR00198##

(564) A regioisomer of monocarbamate was separated and purified by conducting the silica gel column chromatography as described in Example 29, to obtain the title compound (0.73 g, yield 1030%).

(565) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.22 (d, J=6 Hz, 3H), 2.15 (d, J=4 Hz, 1H), 2.81 (d, J=5 Hz, 3H), 4.12 (dd, J=6 Hz, 1H), 4.83 (br s, 1H), 6.00 (d, J=6 Hz, 1H), 7.237.41 (m, 4H)

Example 74

Synthesis of 1-(2-chlorophenyl)-(S)-2-hydroxypropyl-(S)-1-N-propylcarbamate (74)

(566) ##STR00199##

(567) A regioisomer of monocarbamate was separated and purified by conducting the silica gel column chromatography as described in Example 16, to obtain the title compound (0.15 g, yield 1030%).

(568) .sup.1H NMR (400 MHz, CDCl.sub.3) 0.91 (t, J=7 Hz, 3H), 1.22 (d, J=6 Hz, 3H), 1.52 (dd, J=7 Hz, 2H), 2.23 (d, J=4 Hz, 1H), 3.093.21 (m, 2H), 4.094.17 (m, 1H), 4.93 (s, 1H), 5.99 (d, J=6 Hz, 1H), 7.237.47 (m, 4H)

Example 75

Synthesis of 1-(2-chlorophenyl)-(R)-2-hydroxypropyl-(R)-1-N-propylcarbamate (75)

(569) ##STR00200##

(570) A regioisomer of monocarbamate was separated and purified by conducting the silica gel column chromatography as described in Example 23, to obtain the title compound (0.04 g, yield 1030%).

(571) .sup.1H NMR (400 MHz, CDCl.sub.3) 0.91 (t, J=7 Hz, 3H), 1.22 (d, J=6 Hz, 3H), 1.52 (dd, J=7 Hz, 2H), 2.23 (d, J=4 Hz, 1H), 3.093.21 (m, 2H), 4.094.17 (m, 1H), 4.93 (s, 1H), 5.99 (d, J=6 Hz, 1H), 7.237.47 (m, 4H)

Example 76

Synthesis of 1-(2-chlorophenyl)-2-hydroxypropyl-1-N-propylcarbamate (76)

(572) ##STR00201##

(573) A regioisomer of monocarbamate was separated and purified by conducting the silica gel column chromatography as described in Example 30, to obtain the title compound (0.15 g, yield 1030%).

(574) .sup.1H NMR (400 MHz, CDCl.sub.3) 0.91 (t, J=7 Hz, 3H), 1.22 (d, J=6 Hz, 3H), 1.52 (dd, J=7 Hz, 2H), 2.23 (d, J=4 Hz, 1H), 3.093.21 (m, 2H), 4.094.17 (m, 1H), 4.93 (s, 1H), 5.99 (d, J=6 Hz, 1H), 7.237.47 (m, 4H)

Example 77

Synthesis of 1-(2-chlorophenyl)-(S)-2-hydroxypropyl-(S)-1-N-isopropylcarbamate (77)

(575) ##STR00202##

(576) A regioisomer of monocarbamate was separated and purified by conducting the silica gel column chromatography as described in Example 17, to obtain the title compound (0.42 g, yield 1030%).

(577) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.10 (d, J=6.0 Hz, 3H), 1.151.19 (m, 6H), 2.41 (s, 1H), 3.764.08 (m, 1H), 4.34 (s, 1H), 4.83 (br s 1H), 5.95 (d, J=5.3 Hz, 1H), 7.197.39 (m, 4H)

Example 78

Synthesis of 1-(2-chlorophenyl)-(R)-2-hydroxypropyl-(R)-1-N-isopropylcarbamate (78)

(578) ##STR00203##

(579) A regioisomer of monocarbamate was separated and purified by conducting the silica gel column chromatography as described in Example 24, to obtain the title compound (0.5 g, yield 1030%).

(580) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.13 (d, J=6 Hz, 3H), 1.20 (dd, J=9.2 Hz, 6H), 2.23 (s, 1H), 3.773.82 (m, 1H), 4.10 (s, 1H), 4.76 (br s, 1H), 5.98 (d, J=5.6 Hz, 1H), 7.237.41 (m, 4H)

Example 79

Synthesis of 1-(2-chlorophenyl)-2-hydroxypropyl-1-N-isopropylcarbamate (79)

(581) ##STR00204##

(582) A regioisomer of monocarbamate was separated and purified by conducting the silica gel column chromatography as described in Example 31, to obtain the title compound (0.09 g, yield 1030%).

(583) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.14 (d, J=6 Hz, 3H), 1.21 (dd, J=6 Hz, 6H), 2.16 (d, J=5 Hz, 1H), 3.81 (t, J=6 Hz, 1H), 4.11 (d, J=5 Hz, 1H), 4.73 (br s, 1H), 5.98 (d, J=5 Hz, 1H), 7.24741 (m, 4H)

Example 80

Synthesis of 1-(2-chlorophenyl)-(S)-2-hydroxypropyl-(S)-1-N-cyclopropylcarbamate (80)

(584) ##STR00205##

(585) A regioisomer of monocarbamate was separated and purified by conducting the silica gel column chromatography as described in Example 18, to obtain the title compound (0.53 g, yield 1030%).

(586) .sup.1H NMR (400 MHz, CDCl.sub.3) 0.530.60 (m, 2H), 0.74 (s, 2H), 1.21 (d, J=6.0 Hz, 3H), 2.19 (s, 1H), 2.59 (s, 1H), 4.114.15 (m, 1H), 5.13 (br s, 1H), 5.99 (d, J=5.20 Hz, 1H), 7.237.40 (m, 4H)

Example 81

Synthesis of 1-(2-chlorophenyl)-(R)-2-hydroxypropyl-(R)-1-N-cyclopropylcarbamate (81)

(587) ##STR00206##

(588) A regioisomer of monocarbamate was separated and purified by conducting the silica gel column chromatography as described in Example 25, to obtain the title compound (0.58 g, yield 10%).

(589) .sup.1H NMR (400 MHz, CDCl.sub.3) 0.530.60 (m, 2H), 0.74 (s, 2H), 1.21 (d, J=6.0 Hz, 3H), 2.19 (s, 1H), 2.59 (s, 1H), 4.114.15 (m, 1H), 5.13 (br s, 1H), 5.99 (d, J=5.20 Hz, 1H), 7.237.40 (m, 4H)

Example 82

Synthesis of 1-(2-chlorophenyl)-2-hydroxypropyl-1-N-cyclopropylcarbamate (82)

(590) ##STR00207##

(591) A regioisomer of monocarbamate was separated and purified by conducting the silica gel column chromatography as described in Example 32, to obtain the title compound (0.38 g, yield 14%).

(592) .sup.1H NMR (400 MHz, CDCl.sub.3) 0.71 (s, 2H), 1.19 (d, J=6 Hz, 3H), 2.45 (S, 1H), 2.57 (S, 1H), 4.084.12 (m, 1H), 5.26 (s, 1H), 5.97 (d, J=4 Hz, 1H), 7.227.54 (m, 4H)

Example 83

Synthesis of 1-(2-chlorophenyl)-(S)-2-hydroxypropyl-(S)-1-N-cyclohexylcarbamate (83)

(593) ##STR00208##

(594) A regioisomer of monocarbamate was separated and purified by conducting the silica gel column chromatography as described in Example 19, to obtain the title compound (0.24 g, yield 1030%).

(595) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.101.39 (m, 7H), 1.61 (s, 3H), 1.711.74 (m, 2H), 1.87 (d, J=11.2 Hz, 1H), 2.48 (d, J=10.8 Hz, 1H), 3.46 (t, J=4 Hz, 1H), 4.104.11 (m, 1H), 4.80 (br s 1H), 5.97 (d, J=5.6 Hz, 1H), 7.237.41 (m, 4H)

Example 84

Synthesis of 1-(2-chlorophenyl)-(R)-2-hydroxypropyl-(R)-1-N-cyclohexylcarbamate (84)

(596) ##STR00209##

(597) A regioisomer of monocarbamate was separated and purified by conducting the silica gel column chromatography as described in Example 26, to obtain the title compound (0.35 g, yield 10%).

(598) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.101.39 (m, 7H), 1.61 (s, 3H), 1.711.74 (m, 2H), 1.87 (d, J=11.2 Hz, 1H), 2.48 (d, J=10.8 Hz, 1H), 3.46 (t, J=4 Hz, 1H), 4.104.11 (m, 1H), 4.80 (br s 1H), 5.97 (d, J=5.6 Hz, 1H), 7.237.41 (m, 4H)

Example 85

Synthesis of 1-(2-chlorophenyl)-2-hydroxypropyl-1-N-cyclohexylcarbamate (85)

(599) ##STR00210##

(600) A regioisomer of monocarbamate was separated and purified by conducting the silica gel column chromatography as described in Example 33, to obtain the title compound (0.26 g, yield 10%).

(601) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.121.19 (m, 3H), 1.22 (d, J=6 Hz, 3H), 1.271.37 (m, 1H), 1.71 (t, J=6 Hz, 2H), 1.861.88 (m, 1H), 1.972.00 (m, 1H), 2.18 (d, J=4 Hz, 1H), 3.47 (S, 1H), 4.12 (t, J=6 Hz, 1H), 4.78 (S, 1H), 5.97 (d, J=6 Hz, 1H), 7.237.40 (m, 4H)

Example 86

Synthesis of 1-(2-chlorophenyl)-(S)-2-hydroxypropyl-(S)-1-N-benzylcarbamate (86)

(602) ##STR00211##

(603) A regioisomer of monocarbamate was separated and purified by conducting the silica gel column chromatography as described in Example 20, to obtain the title compound (0.19 g, yield 1030%).

(604) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.23 (d, J=6 Hz, 3H), 2.16 (d, J=4 Hz, 1H), 4.12 (t, J=6 Hz, 1H), 4.314.44 (m, 2H), 5.22 (br S, 1H), 6.04 (d, J=6 Hz, 1H), 7.277.42 (m, 9H)

Example 87

Synthesis of 1-(2-chlorophenyl)-(R)-2-hydroxypropyl-(R)-1-N-benzylcarbamate (87)

(605) ##STR00212##

(606) A regioisomer of monocarbamate was separated and purified by conducting the silica gel column chromatography as described in Example 27, to obtain the title compound (0.07 g, yield 1030%).

(607) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.23 (d, J=6 Hz, 3H), 2.16 (d, J=4 Hz, 1H), 4.12 (t, J=6 Hz, 1H), 4.314.44 (m, 2H), 5.22 (br S, 1H), 6.04 (d, J=6 Hz, 1H), 7.277.42 (m, 9H)

Example 88

Synthesis of 1-(2-chlorophenyl)-2-hydroxypropyl-1-N-benzylcarbamate (88)

(608) ##STR00213##

(609) A regioisomer of monocarbamate was separated and purified by conducting the silica gel column chromatography as described in Example 34, to obtain the title compound (0.21 g, yield 14%).

(610) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.23 (d, J=6 Hz, 3H), 2.16 (d, J=4 Hz, 1H), 4.12 (t, J=6 Hz, 1H), 4.314.44 (m, 2H), 5.22 (br S, 1H), 6.04 (d, J=6 Hz, 1H), 7.277.42 (m, 9H)

Example 89

Synthesis of 1-(2,4-dichlorophenyl)-(S)-2-hydroxypropyl-(S)-1-carbamate (89)

(611) ##STR00214##

(612) The substantially same method as described in Example 68 was conducted, except that 1-(2,4-dichlorophenyl)-(S,S)-1,2-propanediol (Preparation example 26) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-propanediol (Preparation example 14), to obtain the title compound (0.05 g, yield 1030%).

(613) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.13 (d, J=6.8 Hz, 3H), 2.49 (d, J=4.0 Hz, 1H), 4.664.74 (m, 1H), 4.76 (br s, 2H), 6.20 (d, J=8.8 Hz, 1H), 7.30 (d, J=8.4 Hz, 1H), 7.39 (d, J=2.0 Hz, 2H), 7.50 (dd, J=8.4 Hz, 2.0 Hz, 1H)

Example 90

Synthesis of 1-(2,6-dichlorophenyl)-(S)-2-hydroxypropyl-(S)-1-carbamate (90)

(614) ##STR00215##

(615) The substantially same method as described in Example 68 was conducted, except that 1-(2,6-dichlorophenyl)-(S,S)-1,2-propanediol (Preparation example 38) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-propanediol (Preparation example 14), to obtain the title compound (0.07 g, yield 24%).

(616) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.13 (d, J=6.8 Hz, 3H), 2.49 (d, J=4.0 Hz, 1H), 4.664.74 (m, 1H), 4.76 (br s, 2H), 6.20 (d, J=8.8 Hz, 1H), 7.257.40 (m, 3H)

Example 91

Synthesis of 1-(2,3-dichlorophenyl)-(S)-2-hydroxypropyl-(S)-1-carbamate (91)

(617) ##STR00216##

(618) The substantially same method as described in Example 68 was conducted, except that 1-(2,3-dichlorophenyl)-(S,S)-1,2-propanediol (Preparation example 57) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-propanediol (Preparation example 14), to obtain the title compound (0.08 g, yield 1030%).

(619) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.15 (d, J=6.4 Hz, 3H), 3.66 (d, J=9.2 Hz, 1H), 4.73 (br s, 2H), 5.43 (t, J=9.0 Hz, 1H), 5.625.69 (m, 1H), 7.187.22 (m, 3H),

Example 92

Synthesis of 1-(2,4-dichlorophenyl)-(S)-2-hydroxybutyl-(S)-1-carbamate (92)

(620) ##STR00217##

(621) The substantially same method as described in Example 68 was conducted, except that 1-(2,4-dichlorophenyl)-(S,S)-1,2-butanediol (Preparation example 29) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-propanediol (Preparation example 14), to obtain the title compound (0.07 g, yield 1030%).

(622) .sup.1H NMR (400 MHz, CDCl.sub.3) 0.77 (t, J=7.4 Hz, 3H), 0.921.01 (m, 1H), 1.181.28 (m, 1H), 4.064.13 (m, 1H), 4.96 (d, J=6.0 Hz, 1H), 5.91 (d, J=8.8 Hz, 1H), 6.4 (br s, 2H), 7.307.50 (m, 3H)

Example 93

Synthesis of 1-(2,6-dichlorophenyl)-(S)-2-hydroxybutyl-(S)-1-carbamate (93)

(623) ##STR00218##

(624) The substantially same method as described in Example 68 was conducted, except that 1-(2,6-dichlorophenyl)-(S,S)-1,2-butanediol (Preparation example 41) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-propanediol (Preparation example 14), to obtain the title compound (0.11 g, yield 29%).

(625) .sup.1H NMR (400 MHz, CDCl.sub.3) 0.77 (t, J=7.4 Hz, 3H), 0.921.01 (m, 1H), 1.181.28 (m, 1H), 4.064.13 (m, 1H), 4.96 (d, J=6.0 Hz, 1H), 5.91 (d, J=8.8 Hz, 1H), 6.4 (br s, 2H), 7.257.40 (m, 3H)

Example 94

Synthesis of 1-(2,4-dichlorophenyl)-(S)-2-hydroxy-3-methyl-butyl-(S)-1-carbamate (94)

(626) ##STR00219##

(627) The substantially same method as described in Example 68 was conducted, except that 1-(2,4-dichlorophenyl)-3-methyl-(S,S)-1,2-butanediol (Preparation example 32) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-propanediol (Preparation example 14), to obtain the title compound (0.01 g, yield 1030%).

(628) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.00 (1, J=7.2 Hz, 6H), 1.731.79 (m, 1H), 3.673.69 (m, 1H), 4.96 (d, J=6.0 Hz, 1H), 5.91 (d, J=8.8 Hz, 1H), 6.42 (br s, 2H), 7.307.50 (m, 3H)

Example 95

Synthesis of 1-(2,6-dichlorophenyl)-(S)-2-hydroxy-3-methyl-butyl-(S)-1-carbamate (95)

(629) ##STR00220##

(630) The substantially same method as described in Example 68 was conducted, except that 1-(2,6-dichlorophenyl)-3-methyl-(S,S)-1,2-butanediol (Preparation example 44) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-propanediol (Preparation example 14), to obtain the title compound (0.03 g, yield 1030%).

(631) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.00 (1, J=7.2 Hz, 6H), 1.731.79 (m, 1H), 3.673.69 (m, 1H), 4.96 (d, J=6.0 Hz, 1H), 5.91 (d, J=8.8 Hz, 1H), 6.42 (br s, 2H), 7.257.40 (m, 3H)

Example 96

Synthesis of 1-(2,4-dichlorophenyl)-(S)-2-hydroxyhexyl-(S)-1-carbamate (96)

(632) ##STR00221##

(633) The substantially same method as described in Example 68 was conducted, except that 1-(2,4-dichlorophenyl)-(S,S)-1,2-hexanediol (Preparation example 35) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-propanediol (Preparation example 14), to obtain the title compound (0.21 g, yield 1030%).

(634) .sup.1H NMR (400 MHz, CDCl.sub.3) 0.85 (t, J=7.2 Hz, 3H), 1.181.33 (m, 4H), 1.481.55 (m, 2H), 2.35 (d, J=4.4 Hz, 1H), 4.454.50 (m, 1H), 4.76 (br s, 2H), 6.21 (d, J=8.4 Hz, 1H), 7.307.50 (m, 3H)

Example 97

Synthesis of 1-(2,6-dichlorophenyl)-(S)-2-hydroxyhexyl-(S)-1-carbamate (97)

(635) ##STR00222##

(636) The substantially same method as described in Example 68 was conducted, except that 1-(2,6-dichlorophenyl)-(S,S)-1,2-hexanediol (Preparation example 47) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-propanediol (Preparation example 14), to obtain the title compound (0.06 g, yield 29%).

(637) .sup.1H NMR (400 MHz, CDCl.sub.3) 0.85 (t, J=7.2 Hz, 3H), 1.181.33 (m, 4H), 1.481.55 (m, 2H), 2.35 (d, J=4.4 Hz, 1H), 4.454.50 (m, 1H), 4.76 (br s, 2H), 6.21 (d, J=8.4 Hz, 1H), 7.167.34 (m, 3H)

Example 98

Synthesis of 1-(2,4-dichlorophenyl)-(R)-2-hydroxypropyl-(R)-1-carbamate (98)

(638) ##STR00223##

(639) The substantially same method as described in Example 68 was conducted, except that 1-(2,4-dichlorophenyl)-(R,R)-1,2-propanediol (Preparation example 27) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-propanediol (Preparation example 14), to obtain the title compound (0.04 g, yield 1030%).

(640) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.13 (d, J=6.8 Hz, 3H), 2.49 (d, J=4.0 Hz, 1H), 4.664.74 (m, 1H), 4.76 (br s, 2H), 6.20 (d, J=8.8 Hz, 1H), 7.307.50 (m, 3H)

Example 99

Synthesis of 1-(2,6-dichlorophenyl)-(R)-2-hydroxypropyl-(R)-1-carbamate (99)

(641) ##STR00224##

(642) The substantially same method as described in Example 68 was conducted, except that 1-(2,6-dichlorophenyl)-(R,R)-1,2-propanediol (Preparation example 39) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-propanediol (Preparation example 14), to obtain the title compound (0.09 g, yield 1030%).

(643) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.13 (d, J=6.8 Hz, 3H), 2.49 (d, J=4.0 Hz, 1H), 4.664.74 (m, 1H), 4.76 (br s, 2H), 6.20 (d, J=8.8 Hz, 1H), 7.257.40 (m, 3H)

Example 100

Synthesis of 1-(2,3-dichlorophenyl)-(R)-2-hydroxypropyl-(R)-1-carbamate (100)

(644) ##STR00225##

(645) The substantially same method as described in Example 68 was conducted, except that 1-(2,3-dichlorophenyl)-(R,R)-1,2-propanediol (Preparation example 58) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-propanediol (Preparation example 14), to obtain the title compound (0.25 g, yield 1030%).

(646) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.15 (d, J=6.4 Hz, 3H), 3.66 (d, J=9.2 Hz, 1H), 4.73 (br s, 2H), 5.43 (t, J=9.0 Hz, 1H), 5.625.69 (m, 1H), 7.187.22 (m, 3H),

Example 101

Synthesis of 1-(2,4-dichlorophenyl)-(R)-2-hydroxybutyl-(R)-1-carbamate (101)

(647) ##STR00226##

(648) The substantially same method as described in Example 68 was conducted, except that 1-(2,4-dichlorophenyl)-(R,R)-1,2-butanediol (Preparation example 30) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-propanediol (Preparation example 14), to obtain the title compound (0.08 g, yield 1030%).

(649) .sup.1H NMR (400 MHz, CDCl.sub.3) 0.77 (t, J=7.4 Hz, 3H), 0.921.01 (m, 1H), 1.181.28 (m, 1H), 4.064.13 (m, 1H), 4.96 (d, J=6.0 Hz, 1H), 5.91 (d, J=8.8 Hz, 1H), 6.4 (br s, 2H), 7.307.50 (m, 3H)

Example 102

Synthesis of 1-(2,6-dichlorophenyl)-(R)-2-hydroxybutyl-(R)-1-carbamate (102)

(650) ##STR00227##

(651) The substantially same method as described in Example 68 was conducted, except that 1-(2,6-dichlorophenyl)-(R,R)-1,2-butanediol (Preparation example 42) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-propanediol (Preparation example 14), to obtain the title compound (0.09 g, yield 1030%). .sup.1H NMR (400 MHz, CDCl.sub.3) 0.77 (t, J=7.4 Hz, 3H), 0.921.01 (m, 1H), 1.181.28 (m, 1H), 4.064.13 (m, 1H), 4.96 (d, J=6.0 Hz, 1H), 5.91 (d, J=8.8 Hz, 1H), 6.4 (br s, 2H), 7.257.40 (m, 3H)

Example 103

Synthesis of 1-(2,4-dichlorophenyl)-(R)-2-hydroxy-3-methyl-butyl-(R)-1-carbamate (103)

(652) ##STR00228##

(653) The substantially same method as described in Example 68 was conducted, except that 1-(2,4-dichlorophenyl)-3-methyl-(R,R)-1,2-propanediol (Preparation example 33) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-propanediol (Preparation example 14), to obtain the title compound (0.01 g, yield 1030%).

(654) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.00 (t, J=7.2 Hz, 6H), 1.731.79 (m, 1H), 3.673.69 (m, 1H), 4.96 (d, J=6.0 Hz, 1H), 5.91 (d, J=8.8 Hz, 1H), 6.42 (br s, 2H), 7.307.50 (m, 3H)

Example 104

Synthesis of 1-(2,6-dichlorophenyl)-(R)-2-hydroxy-3-methyl-butyl-(R)-1-carbamate (104)

(655) ##STR00229##

(656) The substantially same method as described in Example 68 was conducted, except that 1-(2,6-dichlorophenyl)-3-methyl-(R,R)-1,2-propanediol (Preparation example 45) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-propanediol (Preparation example 14), to obtain the title compound (0.01 g, yield 1030%).

(657) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.00 (t, J=7.2 Hz, 6H), 1.731.79 (m, 1H), 3.673.69 (m, 1H), 4.96 (d, J=6.0 Hz, 1H), 5.91 (d, J=8.8 Hz, 1H), 6.42 (br s, 2H), 7.257.40 (m, 3H)

Example 105

Synthesis of 1-(2,4-dichlorophenyl)-(R)-2-hydroxyhexyl-(R)-1-carbamate (105)

(658) ##STR00230##

(659) The substantially same method as described in Example 68 was conducted, except that 1-(2,4-dichlorophenyl)-(R,R)-1,2-hexanediol (Preparation example 36) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-propanediol (Preparation example 14), to obtain the title compound (0.21 g, yield 1030%).

(660) .sup.1H NMR (400 MHz, CDCl.sub.3) 0.85 (t, J=7.2 Hz, 3H), 1.181.33 (m, 4H), 1.481.55 (m, 2H), 2.35 (d, J=4.4 Hz, 1H), 4.454.50 (m, 1H), 4.76 (br s, 2H), 6.21 (d, J=8.4 Hz, 1H), 7.307.50 (m, 3H)

Example 106

Synthesis of 1-(2,6-dichlorophenyl)-(R)-2-hydroxyhexyl-(R)-1-carbamate (106)

(661) ##STR00231##

(662) The substantially same method as described in Example 68 was conducted, except that 1-(2,6-dichlorophenyl)-(R,R)-1,2-hexanediol (Preparation example 48) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-propanediol (Preparation example 14), to obtain the title compound (0.12 g, yield 1030%).

(663) .sup.1H NMR (400 MHz, CDCl.sub.3) 0.85 (t, J=7.2 Hz, 3H), 1.181.33 (m, 4H), 1.481.55 (m, 2H), 2.35 (d, J=4.4 Hz, 1H), 4.454.50 (m, 1H), 4.76 (br s, 2H), 6.21 (d, J=8.4 Hz, 1H), 7.167.34 (m, 3H)

Example 107

Synthesis of 1-(2,4-dichlorophenyl)-2-hydroxypropyl-1-carbamate (107)

(664) ##STR00232##

(665) The substantially same method as described in Example 68 was conducted, except that 1-(2,4-dichlorophenyl)-1,2-propanediol (Preparation example 28) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-propanediol (Preparation example 14), to obtain the title compound (0.05 g, yield 1030%).

(666) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.13 (d, J=6.8 Hz, 3H), 2.49 (d, J=4.0 Hz, 1H), 4.664.74 (m, 1H), 4.76 (br s, 2H), 6.20 (d, J=8.8 Hz, 1H), 7.307.50 (m, 3H)

Example 108

Synthesis of 1-(2,6-dichlorophenyl)-2-hydroxypropyl-1-carbamate (108)

(667) ##STR00233##

(668) The substantially same method as described in Example 68 was conducted, except that 1-(2,6-dichlorophenyl)-1,2-propanediol (Preparation example 40) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-propanediol (Preparation example 14), to obtain the title compound (0.06 g, yield 1030%).

(669) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.13 (d, J=6.8 Hz, 3H), 2.49 (d, J=4.0 Hz, 1H), 4.664.74 (m, 1H), 4.76 (br s, 2H), 6.20 (d, J=8.8 Hz, 1H), 7.257.40 (m, 3H)

Example 109

Synthesis of 1-(2,3-dichlorophenyl)-(R)-2-hydroxypropyl-(R)-1-carbamate (109)

(670) ##STR00234##

(671) The substantially same method as described in Example 68 was conducted, except that 1-(2,3-dichlorophenyl)-1,2-propanediol (Preparation example 59) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-propanediol (Preparation example 14), to obtain the title compound (0.02 g, yield 1030%).

(672) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.15 (d, J=6.4 Hz, 3H), 3.66 (d, J=9.2 Hz, 1H), 4.73 (br s, 2H), 5.43 (t, J=9.0 Hz, 1H), 5.625.69 (m, 1H), 7.187.22 (m, 3H),

Example 110

Synthesis of 1-(2,4-dichlorophenyl)-2-hydroxybutyl-1-carbamate (110)

(673) ##STR00235##

(674) The substantially same method as described in Example 68 was conducted, except that 1-(2,4-dichlorophenyl)-1,2-butanediol (Preparation example 31) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-propanediol (Preparation example 14), to obtain the title compound (0.07 g, yield 1030%).

(675) .sup.1H NMR (400 MHz, CDCl.sub.3) 0.77 (t, J=7.4 Hz, 3H), 0.921.01 (m, 1H), 1.181.28 (m, 1H), 4.064.13 (m, 1H), 4.96 (d, J=6.0 Hz, 1H), 5.91 (d, J=8.8 Hz, 1H), 6.4 (br s, 2H), 7.307.50 (m, 3H)

Example 111

Synthesis of 1-(2,6-dichlorophenyl)-2-hydroxybutyl-1-carbamate (111)

(676) ##STR00236##

(677) The substantially same method as described in Example 68 was conducted, except that 1-(2,6-dichlorophenyl)-1,2-butanediol (Preparation example 43) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-propanediol (Preparation example 14), to obtain the title compound (0.10 g, yield 1030%).

(678) .sup.1H NMR (400 MHz, CDCl.sub.3) 0.77 (t, J=7.4 Hz, 3H), 0.921.01 (m, 1H), 1.181.28 (m, 1H), 4.064.13 (m, 1H), 4.96 (d, J=6.0 Hz, 1H), 5.91 (d, J=8.8 Hz, 1H), 6.4 (br s, 2H), 7.257.40 (m, 3H)

Example 112

Synthesis of 1-(2,4-dichlorophenyl)-2-hydroxy-3-methyl-butyl-1-carbamate (112)

(679) ##STR00237##

(680) The substantially same method as described in Example 68 was conducted, except that 1-(2,4-dichlorophenyl)-3-methyl-1,2-propanediol (Preparation example 34) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-propanediol (Preparation example 14), to obtain the title compound (0.04 g, yield 1030%).

(681) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.00 (t, J=7.2 Hz, 6H), 1.731.79 (m, 1H), 3.673.69 (m, 1H), 4.96 (d, J=6.0 Hz, 1H), 5.91 (d, J=8.8 Hz, 1H), 6.42 (br s, 2H), 7.307.50 (m, 3H)

Example 113

Synthesis of 1-(2,6-dichlorophenyl)-2-hydroxy-3-methyl-butyl-1-carbamate (113)

(682) ##STR00238##

(683) The substantially same method as described in Example 68 was conducted, except that 1-(2,6-dichlorophenyl)-3-methyl-1,2-propanediol (Preparation example 46) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-propanediol (Preparation example 14), to obtain the title compound (0.01 g, yield 1030%).

(684) .sup.1H NMR (400 MHz, CDCl.sub.3) 1.00 (t, J=7.2 Hz, 6H), 1.731.79 (m, 1H), 3.673.69 (m, 1H), 4.96 (d, J=6.0 Hz, 1H), 5.91 (d, J=8.8 Hz, 1H), 6.42 (br s, 2H), 7.257.40 (m, 3H)

Example 114

Synthesis of 1-(2,4-dichlorophenyl)-2-hydroxyhexyl-1-carbamate (114)

(685) ##STR00239##

(686) The substantially same method as described in Example 68 was conducted, except that 1-(2,4-dichlorophenyl)-1,2-hexanediol (Preparation example 37) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-propanediol (Preparation example 14), to obtain the title compound (0.21 g, yield 1030%).

(687) .sup.1H NMR (400 MHz, CDCl.sub.3) 0.85 (t, J=7.2 Hz, 3H), 1.181.33 (m, 4H), 1.481.55 (m, 2H), 2.35 (d, J=4.4 Hz, 1H), 4.454.50 (m, 1H), 4.76 (br s, 2H), 6.21 (d, J=8.4 Hz, 1H), 7.307.50 (m, 3H)

Example 115

Synthesis of 1-(2,6-dichlorophenyl)-2-hydroxyhexyl-1-carbamate (115)

(688) ##STR00240##

(689) The substantially same method as described in Example 68 was conducted, except that 1-(2,6-dichlorophenyl)-1,2-hexanediol (Preparation example 49) was used instead of 1-(2-chlorophenyl)-(S,S)-1,2-propanediol (Preparation example 14), to obtain the title compound (0.12 g, yield 1030%).

(690) .sup.1H NMR (400 MHz, CDCl.sub.3) 0.85 (t, J=7.2 Hz, 3H), 1.181.33 (m, 4H), 1.481.55 (m, 2H), 2.35 (d, J=4.4 Hz, 1H), 4.454.50 (m, 1H), 4.76 (br s, 2H), 6.21 (d, J=8.4 Hz, 1H), 7.167.34 (m, 3H)

(691) Compounds 1 to 115 produced in Examples 1 to 115 were summarized in following Tables 1 and 2.

(692) TABLE-US-00001 TABLE 1 Compounds 1 to 67 having the structure of Chemical Formula 1 where A is a carbamoyl derivative and B is H A A = carbamoyl n derivative B No. X (position) 1.sup.st Chiral 2.sup.nd Chiral R.sup.1 R.sup.2 = B = H 1 Cl 1(2-) S S Me H H 2 Cl 1(2-) R R Me H H 3 Cl 1(2-) Rac. Rac. Me H H 4 Cl 1(2-) S R Me H H 5 Cl 1(2-) R S Me H H 6 Cl 1(2-) S S Et H H 7 Cl 1(2-) R R Et H H 8 Cl 1(2-) Rac. Rac. Et H H 9 Cl 1(2-) S S Isopropyl H H 10 Cl 1(2-) R R Isopropyl H H 11 Cl 1(2-) Rac. Rac. Isopropyl H H 12 Cl 1(2-) S S butyl H H 13 Cl 1(2-) R R butyl H H 14 Cl 1(2-) Rac. Rac. butyl H H 15 Cl 1(2-) S S Me Me H 16 Cl 1(2-) S S Me Propyl H 17 Cl 1(2-) S S Me Isopropyl H 18 Cl 1(2-) S S Me Cyclopropyl H 19 Cl 1(2-) S S Me Cyclohexyl H 20 Cl 1(2-) S S Me Benzyl H 21 Cl 1(2-) S S Me Bicyclo[2.2.1]heptane H 22 Cl 1(2-) R R Me Me H 23 Cl 1(2-) R R Me Propyl H 24 Cl 1(2-) R R Me Isopropyl H 25 Cl 1(2-) R R Me Cyclopropyl H 26 Cl 1(2-) R R Me Cyclohexyl H 27 Cl 1(2-) R R Me Benzyl H 28 Cl 1(2-) R R Me Bicyclo[2.2.1]heptane H 29 Cl 1(2-) Rac. Rac. Me Me H 30 Cl 1(2-) Rac. Rac. Me Propyl H 31 Cl 1(2-) Rac. Rac. Me Isopropyl H 32 Cl 1(2-) Rac. Rac. Me Cyclopropyl H 33 Cl 1(2-) Rac. Rac. Me Cyclohexyl H 34 Cl 1(2-) Rac. Rac. Me Benzyl H 35 Cl 1(2-) Rac, Rac. Me Bicyclo[2.2.1]heptane H 36 Cl 2(2,4-) S S Me H H 37 Cl 2(2,6-) S S Me H H 38 Cl 2(2,3-) S S Me H H 39 Cl 2(2,4-) S S Et H H 40 Cl 2(2,6-) S S Et H H 41 Cl 2(2,4-) S S Isopropyl H H 42 Cl 2(2,6-) S S Isopropyl H H 43 Cl 2(2,4-) S S butyl H H 44 Cl 2(2,6-) S S butyl H H 45 Cl 2(2,4-) R R Me H H 46 Cl 2(2,6-) R R Me H H 47 Cl 2(2,3-) R R Me H H 48 Cl 2(2,4-) R R Et H H 49 Cl 2(2,6-) R R Et H H 50 Cl 2(2,4-) R R Isopropyl H H 51 Cl 2(2,6-) R R Isopropyl H H 52 Cl 2(2,4-) R R butyl H H 53 Cl 2(2,6-) R R butyl H H 54 Cl 2(2,4-) Rac, Rac. Me H H 55 Cl 2(2,6-) Rac, Rac. Me H H 56 Cl 2(2,3-) Rac, Rac. Me H H 57 Cl 2(2,4-) Rac, Rac. Et H H 58 Cl 2(2,6-) Rac, Rac. Et H H 59 Cl 2(2,4-) Rac, Rac. Isopropyl H H 60 Cl 2(2,6-) Rac, Rac. Isopropyl H H 61 Cl 2(2,4-) Rac, Rac. butyl H H 62 Cl 2(2,6-) Rac, Rac. butyl H H 63 F 1(2-) S S Me H H 64 F 1(2-) R R Me H H 65 I 1(2-) S S Me H H 66 I 1(2-) R R Me H H 67 I 1(2-) S S Et H H

(693) TABLE-US-00002 TABLE 2 Compounds 68 to 115 having the structure of Chemical Formula 1 where A is H and B is a carbamoyl derivative B B = n A carbamoyl (po- 1.sup.st 2.sup.nd A = derivative No. X sition) Chiral Chiral R.sup.1 H R.sup.3= 68 Cl 1(2-) S S Me H H 69 Cl 1(2-) R R Me H H 70 Cl 1(2-) Rac. Rac. Me H H 71 Cl 1(2-) S S Me H Me 72 Cl 1(2-) R R Me H Me 73 Cl 1(2-) Rac. Rac. Me H Me 74 Cl 1(2-) S S Me H Propyl 75 Cl 1(2-) R R Me H Propyl 76 Cl 1(2-) Rac. Rac. Me H Propyl 77 Cl 1(2-) S S Me H Isopropyl 78 Cl 1(2-) R R Me H Isopropyl 79 Cl 1(2-) Rac. Rac. Me H Isopropyl 80 Cl 1(2-) S S Me H Cyclopropyl 81 Cl 1(2-) R R Me H Cyclopropyl 82 Cl 1(2-) Rac. Rac. Me H Cyclopropyl 83 Cl 1(2-) S S Me H Cyclohexyl 84 Cl 1(2-) R R Me H Cyclohexyl 85 Cl 1(2-) Rac. Rac. Me H Cyclohexyl 86 Cl 1(2-) S S Me H Benzyl 87 Cl 1(2-) R R Me H Benzyl 88 Cl 1(2-) Rac. Rac. Me H Benzyl 89 Cl 2(2,4-) S S Me H H 90 Cl 2(2,6-) S S Me H H 91 Cl 2(2,3-) S S Me H H 92 Cl 2(2,4-) S S Et H H 93 Cl 2(2,6-) S S Et H H 94 Cl 2(2,4-) S S Isopropyl H H 95 Cl 2(2,6-) S S Isopropyl H H 96 Cl 2(2,4-) S S Butyl H H 97 Cl 2(2,6-) S S Butyl H H 98 Cl 2(2,4-) R R Me H H 99 Cl 2(2,6-) R R Me H H 100 Cl 2(2,3-) R R Me H H 101 Cl 2(2,4-) R R Et H H 102 Cl 2(2,6-) R R Et H H 103 Cl 2(2,4-) R R Isopropyl H H 104 Cl 2(2,6-) R R Isopropyl H H 105 Cl 2(2,4-) R R Butyl H H 106 Cl 2(2,6-) R R Butyl H H 107 Cl 2(2,4-) Rac. Rac. Me H H 108 Cl 2(2,6-) Rac. Rac. Me H H 109 Cl 2(2,3-) Rac. Rac. Me H H 110 Cl 2(2,4-) Rac. Rac. Et H H 111 Cl 2(2,6-) Rac. Rac. Et H H 112 Cl 2(2,4-) Rac. Rac. Isopropyl H H 113 Cl 2(2,6-) Rac. Rac. Isopropyl H H 114 Cl 2(2,4-) Rac. Rac. Butyl H H 115 Cl 2(2,6-) Rac. Rac. Butyl H H

Biological Experimental Example 1

Measurement of Anti-Epilepsy Activity

(694) In the MES test (Ref., G. Villetti et al. Neuropharmacology 40 (2001) 866-878), an electrical stimulus (mice; 50 mA, 60 Hz, 0.2 sec and rats; 150 mA 60 Hz, 0.2 sec in the test animal) supplied by 11A Shocker (IITC Life Science Company) was delivered through corneal electrodes. All mice or rats assigned to any electroshock at peak time were treated with each test compound sample which was dissolved in 30% PEG400 prepared by saline solvent applied to oral before the test. If the test animal stretching their hind limb in a straight line weren't observed in the MES test, the results indicate that the test sample had an anti-epilepsy activity. Three doses of the test sample were administered orally to over 18 mice (6 mice per dose) for evaluating the respective doses at which 50% of the animals are protected from seizure (ED50). The value of ED50 (median effective dose) is calculated by Litchfield and Wicoxon log-probit method which is a dose-response relationship. Then, the test results are shown in following Table 3. Experimental animal, male ICR mice and male SD rats, were purchased from OrientBio or Nara biotech, Korea, and housed 4-5 mice per a cage for 4-5 days. The range of mice body weight was used between 19 and 26 grams and range of rats body weight was used between 100 and 130 grams.

Biological Experimental Example II

Measurement of Anti-Epilepsy Activity Through scPTZ

(695) In this experiment, each test compound sample was formulated as described in Biological Experimental Example I, and administered intraperitoneally to test animals (mice; ICR or Rat; SD); Experimental animal, male ICR mice and male SD rats, were purchased from OrientBio or Nara biotech, Korea, and housed 4-5 mice per a cage for 4-5 days. The range of mice body weight was used between 19 and 26 grams and range of rats body weight was used between 100 and 130 grams. After Peak time (0.5, 1, 2 and 4 hr) from the administration, PTZ (Pentylenetetrazol) was administered subcutaneously in the concentration capable of inducing 97% intermittent convulsions (mice: 100110 mg/kg.Math.bw, 100 ul/g, or rats: 90110 mg/kg.Math.bw, 20 ul/g). If clonic seizure was not observed for at least 3 seconds in the PTZ administered animal, it can be considered that the test compound has anti-epilepsy activity. The median effective dose (ED50) is determined using 6 animals per a concentration (total three different concentrations), and calculated by Litchfield and Wicoxon log-probit method which is a dose-response relationship. The obtained results are shown in following Table 3.

Biological Experimental Example III

Measurement of Neurotoxicity

(696) The measurement of neurotoxicity of the test compounds was conducted by the method of Dunham and Miya [Dunham, N. W. and Miya, T. S. 1957. A note on a simple apparatus for detecting neurological deficit in rats and mice. J. Am. Pharm. Assoc. (Baltimore) 46: 208-209]. In the method, motor abilities of the test animals can be determined by observing whether the test animals can walk without falling from a rotator, thereby determining the value of neurotoxicity of each compound. Term TD50 means the respective dose of the test compound at which 50% of the test animal exhibit neurotoxicity. They were pre-trained on the rotarod (Rotarod; Columbus instrument, rota-max, USA) at 6 rpm for 5 min 24 hr prior to the test. The peak time was determined by administration test material's random dose for 0.5, 1, 2, 4 hour. To evaluate the minimal neurotoxicity of the compound, the mice were placed on the Rotarod (rod circle; 3 Cm) at 6 rpm and the test animal fails to maintain walking once or more during 1 minute, it can be regarded that the test animal exhibits neurotoxicity. The ratio of TD50 to ED50 (TD50/ED50) is called as a protective index, and useful as a parameter for comparison of pharmaceutical efficacy and neurotoxicity. The obtained results are shown in following Table 3.

(697) [Statistical Analysis]

(698) The obtained results are shown as meansem. The difference between the groups was statistically analyzed by ANOVA, and then, further examined by Dunnett's test or Bonferroni test. If p is less than 0.05, it was determined that the difference between the groups had statistical significance.

(699) TABLE-US-00003 TABLE 3 Measurement results of anti-epilepsy activity of compounds in the test animals (Mice and Rats) MES test(po) ScPTZ test(ip) Peak Peak TD50 PI (TD50/ Compound ED50 Time ED50 Time (mg/kg ED50 in No. (mg/kg) (h) (mg/kg) (h) po) MES) 1 13.0 2 15.8 2 218.1 16.8 2 51.0 0.25 38.8 0.5 372.0 7.3 3 31.4 2 15.3 0.5 378.3 12.0 4 82.4 0.5 5 84.1 0.5 15.0 0.5 275.2 3.3 6 22.2 1 17.9 0.5 8 100.sup.a(100%) 9 67.1 0.5 12 100.sup.a(75%) 13 200.sup.a(75%) 14 200.sup.a(100%) 15 100.sup.a(75%) 16 200.sup.a(25%) 18 200.sup.a(100%) 23 200.sup.a(25%) 25 200.sup.a(25%) 29 200.sup.a(75%) 30 200.sup.a(25%) 31 200.sup.a(25%) 32 200.sup.a(100%) 36 82.8 37 25.8 0.25 25.7 0.25 131.6 5.1 38 91.4 2 39 41.2 1 24.3 0.5 40 46.9 42 35.2 0.5 43 100.sup.a(25%) 44 100.sup.a(75%) 45 200.sup.a(0%) 46 35.2 1 63 50.sup.a(100%) 65 50.sup.a(100%) 67 100.sup.a(100%) # a: Injection amount(mg/kg), Protection % (4 mice); b: Injection amount(mg/kg), Protection % (6 Rats);

Biological Experimental Example IV

Measurement of Pharmaceutical Efficacy Duration Time Through MES

(700) The ED50 values according to time were measured in the test animals (mice and rats) after oral administration of test compound 1 as described in Biological Experimental Example I. The obtained results are shown in following Table 4 and FIG. 1.

(701) TABLE-US-00004 TABLE 4 Duration of MES test ED50 (mg/kg), (po) Time No species 0.25 h 0.5 h 1 h 2 h 3 h 4 h 6 h 8 h 12 h 1 Mouse 21.2 22.5 13.3 13.0 14.7 18.7 30.0 49.4 118.8 Rat 5.9 3.3 1.4 6.9 14.4 36.1

(702) As shown in Table 4 and FIG. 1, the test compound 1 exhibits the efficacy duration time of at least 12 hours in both of the tested rats and mice.

Biological Experimental Example V

Measurement of Pharmaceutical Efficacy Duration Time Through scPTZ

(703) The ED50 values according to time were measured in the test animals (mice and rats) after intraperitoneal administration of test compound 1 as described in Biological Experimental Example II. The obtained results are shown in following Table 5 and FIG. 2.

(704) TABLE-US-00005 TABLE 5 Duration of scPTZ test ED50 (mg/kg), (ip) Time No species 0.5 h 1 h 2 h 4 h 6 h 8 h 12 h 1 Mouse 17.3 16.9 15.8 27.4 52.2 80.7 201.1 Rat 18.9 14.5 21.0 31.0 41.3 76.7

(705) As shown in Table 5 and FIG. 2, the test compound 1 exhibits the efficacy duration time of at least 12 hours in both of the tested rats and mice.

(706) As the pharmaceutical efficacy duration time of a drug is longer, the administration number of the drug becomes decreased, thereby increasing the administration convenience of a patient. Such advantages may be particularly preferable for a patient suffered from a disease that requires long term administration of a drug, such as epilepsy. In addition, the decrease of the administration number may be profitable in economic aspect and helpful to increase the quality of life of the patient.