Diester compound having a dimethylcyclobutane ring, a process for preparing the same, and a process for preparing dimethylcyclobutane compound derived from the diester compound

Abstract

The present invention provides a process for preparing a diester compound of the following general formula (1), having a dimethylcyclobutane ring, wherein R.sup.1 and R.sup.2 represent, independently of each other, a monovalent hydrocarbon group having 1 to 10 carbon atoms, the process comprising reacting a dimethylcyclobutanone compound of the following general formula (2), wherein R.sup.1 is as defined above, with a phosphonic ester compound of the following general formula (3), wherein R.sup.2 and R.sup.3 represent, independently of each other, a monovalent hydrocarbon group having 1 to 10 carbon atoms, to produce the diester compound (1), having a dimethylcyclobutane ring. ##STR00001##

Claims

1. A diester compound of general formula (1), having a dimethylcyclobutane ring, ##STR00059## wherein R.sup.1 and R.sup.2 represent, independently of each other, a monovalent hydrocarbon group having 1 to 10 carbon atoms.

2. A process for preparing the diester compound of claim 1 of general formula (1), having a dimethylcyclobutane ring, ##STR00060## wherein R.sup.1 and R.sup.2 represent, independently of each other, a monovalent hydrocarbon group having 1 to 10 carbon atoms, the process comprising reacting a dimethylcyclobutanone compound of general formula (2): ##STR00061## wherein R.sup.1 is as defined above, with a phosphonic ester compound of general formula (3):
R.sup.2O.sub.2C—(CH.sub.3)CH—P(O)(OR.sup.3).sub.2  (3) wherein R.sup.2 is as defined above, and R.sup.3 represents a monovalent hydrocarbon group having 1 to 10 carbon atoms, to produce the diester compound (1), having a dimethylcyclobutane ring.

3. A process for preparing a diol compound of formula (4), having a dimethylcyclobutane ring, ##STR00062## the process comprising subjecting the diester compound of claim 2 of general formula (1), having a dimethylcyclobutane ring, ##STR00063## wherein R.sup.1 and R.sup.2 represent, independently of each other, a monovalent hydrocarbon group having 1 to 10 carbon atoms, to a reduction reaction to produce the diol compound (4), having a dimethylcyclobutane ring.

4. The diester compound of claim 3 of general formula (1), wherein the diester compound has a chemical structure selected from the following: ##STR00064## ##STR00065##

Description

EXAMPLES

(1) The present invention will be further described with reference to the following Examples. It should be understood that the present invention is not limited to or by the Examples.

(2) A sample for measuring the spectrum was obtained by purifying a crude product in some cases.

(3) A crude yield refers to a yield of a crude product without being purified.

Example 1

Preparation of Ethyl 3-(1-ethoxycarbonylethylidene)-2,2-dimethylcyclobutanecarboxylate

(4) ##STR00035##

(5) Sodium hydride (5.33 g, 0.222 mol) and tetrahydrofuran (THF) (500 g) were placed in a reactor in a nitrogen atmosphere and stirred at 10° C. to prepare a suspension. A solution of triethyl 2-phosphonopropionate (52.9 g, 0.222 mol) in THF (16 g) was added dropwise to the suspension at internal temperature in the reactor of 20° C. or below. After the completion of the dropwise addition, the suspension was stirred at 55° C. for 1 hour. Next, a solution of ethyl 2,2-dimethyl-3-oxocyclobutanecarboxylate (32.9 g, 0.193 mol) in THF (30 g) was added dropwise at internal temperature in the reactor of 60° C. or below and were stirred under reflux for 9 hours. Subsequently, water was added to the reaction mixture, and the organic layer was separated and subjected to post-treatment by ordinary washing, drying and concentration. Then, the obtained concentrated liquid was subjected to distillation at a reduced pressure to obtain the target compound, ethyl 3-(1-ethoxycarbonylethylidene)-2,2-dimethylcyclobutanecarboxylate, as a geometric isomer mixture at E:Z=57:43 (38.3 g, 0.150 mol) in a yield of 78%.

(6) The following is spectrum data of ethyl (E)-3-(1-ethoxycarbonylethylidene)-2,2-dimethylcyclobutanecarboxylate thus produced (colorless or pale yellow oily liquid) thus produced.

(7) IR (D-ATR): νmax=2965, 2933, 2870, 1732, 1705, 1674, 1463, 1448, 1387, 1367, 1343, 1305, 1282, 1250, 1185, 1160, 1111, 1038, 861,767 cm.sup.−1.

(8) .sup.1H-NMR (500 MHz CDCl.sub.3): δ=1.18 (3H, s), 1.22-1.28 (6H, m), 1.41 (3H, s), 1.77 (3H, t, J=2.1 Hz), 2.83 (1H, dd, J=8.0, 9.2 Hz), 3.03-3.11 (1H, m), 3.27-3.35 (1H, m), 4.10-4.21 (4H, m) ppm.

(9) .sup.13C-NMR (150 MHz, CDCl.sub.3): δ 13.16, 14.31, 14.42, 21.11, 26.88, 30.86, 45.64, 48.25, 60.02, 60.27, 120.12, 160.91, 168 0.09, 172.82 ppm.

(10) The following is spectrum data of ethyl (Z)-3-(1-ethoxycarbonylethylidene)-2,2-dimethylcyclobutanecarboxylate (colorless or pale yellow oily liquid) thus produced.

(11) IR (D-ATR): νmax=2981, 2961, 2930, 2870, 1732, 1715, 1671, 1449, 1371, 1342, 1301, 1280, 1247, 1185, 1156, 1114, 1095, 1077, 1049, 860, 772 cm.sup.−1.

(12) .sup.1H-NMR (500 MHz CDCl.sub.3): δ=1.23 (3H, s), 1.26 (3H, t, J=7.3 Hz), 1.28 (3H, t, J 7.3 Hz), 1.42 (3H, s), 1.69 (3H, t, J=1.5 Hz), 2.64-2.71 (1H, m), 2.81 (1H, dd, J=7.6, 8.8 Hz), 3.01-3.08 (1H, m), 4.09-4.22 (4H, m) ppm.

(13) .sup.13C-NMR (150 MHz, CDCl.sub.3): δ=14.19, 14.31, 14.41, 20.73, 26.59, 27.84, 44.85, 49.80, 59.99, 60.29, 120.38, 159.90, 166.68, 172.93 ppm.

Example 2

Preparation of 2-(3-hydroxymethyl-2,2-dimethylcyclobutylidene)propan-1-ol

(14) ##STR00036##

(15) A solution of 1.01 M diisobutylaluminum hydride (DIBAL) in toluene (1 L, 1.01 mol) was placed in a reactor in a nitrogen atmosphere and stirred at −60° C. A solution of the geometric isomer mixture of E:Z=57:43 of ethyl 3-(1-ethoxycarbonylethylidene)-2,2-dimethylcyclobutanecarboxylate (36.6 g, 0.144 mol) obtained as in Example 1 in tetrahydrofuran (THF) (80 g) was added dropwise to the solution at internal temperature in the reactor of −50° C. or below. After the completion of the dropwise addition, the temperature of the mixture was gradually elevated up to 10° C., and then the mixture was stirred for 5 hours. Subsequently, a saturated aqueous solution of Rochelle salt was added to the mixture, and the organic layer was separated and subjected to post-treatment by ordinary washing, drying and concentration to obtain the target crude compound, 2-(3-hydroxymethyl-2,2-dimethylcyclobutylidene)propan-1-ol, as a geometric isomer mixture at E:Z=57:43 (24.5 g, 0.144 mol) in a crude yield of 100%.

(16) The following is spectrum data of (E)-2-(3-hydroxymethyl-2,2-dimethylcyclobutylidene)propan-1-ol (colorless or pale yellow oily liquid) thus produced.

(17) IR (D-ATR): νmax=3322, 2955, 2922, 2864, 1703, 1459, 1382, 1361, 1311, 1276, 1224, 1167, 1101, 1053, 1031, 1005, 942, 886 cm.sup.−1.

(18) .sup.1H-NMR (500 MHz CDCl.sub.3): δ=1.18 (3H, s), 1.28 (3H, s), 1.66 (3H, t, J=1.9 Hz), 1.76 (2H, brs), 2.06-2.13 (1H, m), 2.19-2.26 (1H, m), 2.66-2.72 (1H, m), 3.61 (1H, dd, J=7.2, 10.7 Hz), 3.75 (1H, dd, J=7.6, 10.7 Hz), 3.89 (2H, brs) ppm.

(19) .sup.13C-NMR (150 MHz, CDCl.sub.3): δ 14.19, 20.51, 27.54, 28.24, 42.71, 44.40, 63.78, 63.88, 125.64, 142.47 ppm.

(20) The following is spectrum data of (Z)-2-(3-hydroxymethyl-2,2-dimethylcyclobutylidene)propan-1-ol (colorless or pale yellow oily liquid) thus produced.

(21) IR (D-ATR): νmax=3329, 2954, 2925, 2865, 1702, 1445, 1374, 1362, 1312, 1272, 1249, 1166, 1121, 1066, 1026, 1003, 888 cm.sup.−1.

(22) .sup.1H-NMR (500 MHz CDCl.sub.3): δ=1.18 (3H, s), 1.28 (3H, s), 1.56 (3H, t, J 1.3 Hz), 1.57 (2H, brs), 2.07-2.23 (2H, m), 2.59-2.65 (1H, m), 3.62 (1H, dd, J=6.8, 10.7 Hz), 3.76 (1H, dd, J=7.6, 10.7 Hz), 3.98-4.05 (2H, m) ppm.

(23) .sup.13C-NMR (150 MHz, CDCl.sub.3): δ=15.07, 21.90, 27.63, 29.56, 42.49, 44.58, 62.51, 63.97, 126.32, 143.79 ppm.

Example 3

Preparation of [3-(2-acetoxy-1-methylethylidene)-2,2-dimethylcyclobutyl]methyl Acetate

(24) ##STR00037##

(25) A geometric isomer mixture of E:Z 57:43 of 2-(3-hydroxymethyl-2,2-dimethylcyclobutylidene)propan-1-ol (24.5 g, 0.144 mol) obtained in Example 2, toluene (202 g), and pyridine (114 g, 1.44 mol) were placed in a reactor in a nitrogen atmosphere and stirred at 10° C. Acetic anhydride (73.6 g, 0.721 mol) was added dropwise to the solution at internal temperature in the reactor of 20° C. or below. After the completion of the dropwise addition, the mixture was stirred at 15° C. for 6 hours. Subsequently, water was added to the mixture, and the organic layer was separated and subjected to post-treatment by ordinary washing, drying and concentration. Then, the obtained concentrated liquid was subjected to distillation at a reduced pressure to obtain the target compound, [3-(2-acetoxy-1-methylethylidene)-2,2-dimethylcyclobutyl]methyl acetate, as a geometric isomer mixture at E:Z=57:43 (30.0 g, 0.118 mol) in a yield of 82%.

(26) The following is spectrum data of [(E)-3-(2-acetoxy-1-methylethylidene)-2,2-dimethylcyclobutyl]methyl acetate (colorless or pale yellow oily liquid) thus produced.

(27) IR (D-ATR): νmax 2958, 1740, 1459, 1380, 1365, 1235, 1171, 1023, 974, 893, 830, 605 cm.sup.−1.

(28) .sup.1H-NMR (500 MHz CDCl.sub.3): δ=1.16 (3H, s), 1.27 (3H, s), 1.61 (3H, t, J=1.9 Hz), 2.02 (3H, s), 2.04 (3H, s)), 2.20-2.29 (2H, m), 2.68-2.75 (1H, m), 4.06-4.14 (2H, m), 4.32 (1H, d, J=11.8 Hz), 4.35 (1H, d, J=11.8 Hz) ppm.

(29) .sup.13C-NMR (150 MHz, CDCl.sub.3): δ=14.51, 20.54, 20.92, 20.95, 27.72, 27.85, 39.05, 44.62, 65.25, 65.31, 121.57, 144.58, 171.06, 171.11 ppm.

(30) The following is spectrum data of [(Z)-3-(2-acetoxy-1-methylethylidene)-2,2-dimethylcyclobutyl]methyl acetate (colorless or pale yellow oily liquid) thus produced.

(31) IR (D-ATR): νmax=2957, 1741, 1462, 1366, 1236, 1024, 975, 891, 631, 606 cm.sup.−1.

(32) .sup.1H-NMR (500 MHz CDCl.sub.3): δ=1.15 (3H, s), 1.26 (3H, s), 1.51-1.52 (3H, m), 2.02 (3H, s), 2.04 (3H, s), 2.17-2.27 (2H, m), 2.61-2.69 (1H, m), 4.09 (1H, d, J=5.4 Hz), 4.12 (1H, d, J 5.4 Hz), 4.47 (2H, brs) ppm.

(33) .sup.13C-NMR (150 MHz, CDCl.sub.3): δ=15.46, 20.91, 29.94, 21.65, 27.80, 28.82, 38.88, 44.79, 64.06, 65.23, 121.91, 145.70, 171 0.05, 171.14 ppm.

Example 4

Preparation of [3-[2-(2-methylbutanoyloxy)-1-methylethylidene]-2,2-dimethylcyclobutyl]methyl 2-methylbutanoate

(34) ##STR00038##

(35) A geometric isomer mixture of E:Z=57:43 of 2-(3-hydroxymethyl-2,2-dimethylcyclobutylidene)propan-1-ol (1.72 g, 10.1 mmol) obtained as in Example 2, tetrahydrofuran (THF) (36 g), and pyridine (16 g, 0.202 mol) were placed in a reactor in a nitrogen atmosphere and stirred at 0° C. for 1 hour. 2-Methylbutanoyl chloride (4.85 g, 40.2 mmol) was added dropwise to the solution at internal temperature in the reactor of 20° C. or below. After the completion of the dropwise addition, the mixture was stirred at 20° C. for 3 hours. Subsequently, water was added to the mixture, and the organic layer was separated and subjected to post-treatment by ordinary washing, drying and concentration. Then, the obtained concentrated liquid was purified by silica gel column chromatography (hexane:ethyl acetate=30:1) to obtain the target compound, [3-[2-(2-methylbutanoyloxy)-1-methylethylidene]-2,2-dimethylcyclobutyl]methyl 2-methylbutanoate, as a geometric isomer mixture at E:Z=51:43 (1.88 g, 5.56 mmol) in a yield of 55%.

(36) The following is spectrum data of [3-[2-(2-methylbutanoyloxy)-1-methylethylidene]-2,2-dimethylcyclobutyl]methyl 2-methylbutanoate (colorless or pale yellow oily liquid) thus produced.

(37) .sup.1H-NMR (500 MHz CDCl.sub.3): δ=0.87-0.91 (6H, m), 1.12 (3H, d, J=4.2 Hz), 1.13 (3H, d, J=4.6 Hz), 1.14, 1.16 (3H, s, s), 1.26, 1.27 (3H, s, s), 1.40-1.52, 1.61-1.72 (7H, m), 2.19-2.41 (4H, m), 2.62-2.76 (1H, m), 4.08-4.27 (2H, m), 4.32-4.40, 4.44-4.50 (2H, m) ppm.

Example 5

Preparation of 1-chloromethyl-3-(2-chloro-1-methylethylidene)-2,2-dimethylcyclobutane

(38) ##STR00039##

(39) A geometric isomer mixture of E:Z=57:43 of 2-(3-hydroxymethyl-2,2-dimethylcyclobutylidene)propan-1-ol (1.64 g, 9.61 mmol) obtained as in Example 2 and carbon tetrachloride (48 g, 0.31 mol) were placed in a reactor in a nitrogen atmosphere and stirred at 0° C. Subsequently, triphenylphosphine (7.56 g, 28.8 mmol) was added, and the mixture was stirred for 24 hours, while heated gradually to a temperature of 20° C. Subsequently, methanol (5 g) was added to the reaction mixture at an ambient temperature, and stirred for 1 hour. The reaction mixture was concentrated, followed by addition of hexane and removal of the precipitate by filtration. The filtrate was concentrated, and the concentrate was purified by silica gel column chromatography (hexane) to obtain the target compound, 1-chloromethyl-3-(2-chloro-1-methylethylidene)-2,2-dimethylyclobutane, as a geometric isomer mixture at E:Z=57:43 (1.06 g, 5.13 mmol) in a yield of 53%.

(40) The following is spectrum data of 1-chloromethyl-3-(2-chlor-1-methylethylidene)-2,2-dimethylyclobutane (colorless or pale yellow oily liquid) thus produced.

(41) .sup.1H-NMR (500 MHz CDCl.sub.3): δ=1.20, 1.23 (3H, s), 1.31, 1.35 (3H, s), 1.59, 1.71 (3H, m), 2.21-2.37 (2H, m), 2.70-2.85 (1H, m), 3.50-3.54 (1H, m), 3.61-3.66 (1H, m), 3.89, 4.02 (2H, m) ppm.

Example 6

Preparation of [2-(3-hydroxymethyl-2,2-dimethylcyclobutylidene)propyl]triphenylphosphonium Bromide

(42) ##STR00040##

(43) A geometric isomer mixture of E:Z=57:43 of 2-(3-hydroxymethyl-2,2-dimethylcyclobutylidene)propan-1-ol (300 mg, 1.76 mmol) obtained as in Example 2, acetonitrile (12 g), and triphenylphosphine hydrobromide (670 mg, 1.95 mmol) were placed in a reactor in a nitrogen atmosphere and stirred under reflux for 5 hours. Pyridine (1 g) was added to a solution of the obtained [2-(3-hydroxymethyl-2,2-dimethylcyclobutylidene)propyl]triphenylphosphonium bromide, and the mixture was concentrated at a reduced pressure. Next, toluene (12 g) was added to the concentrated solution, and concentration at a reduced pressure was carried out twice to obtain the target crude compound, [2-(3-hydroxymethyl-2,2-dimethylcyclobutylidene)propyl]triphenylphosphonium bromide, (872 mg, 1.76 mmol) in a crude yield of 100%.

(44) The following is spectrum data of [2-(3-hydroxymethyl-2,2-dimethylcyclobutylidene)propyl]triphenylphosphonium bromide (colorless or pale yellow oily liquid) thus produced.

(45) .sup.1H-NMR (500 MHz CD.sub.3CN): δ=0.72, 1.06 (3H, a), 0.85, 1.17 (3H, s), 1.28-1.32, 1.43-1.47 (3H, m), 1.47-2.70 (3H, m), 3.18-3.22, 3.32-3.46 (2H, m), 3.83, 3.91 (2H, d, J=14.6 Hz, d, J 14.6 Hz), 7.26-7.92 (15H, m) ppm.

Example 7

Preparation of [2,2-dimethyl-3-(2-bromo-1-methylethylidene)cyclobutyl]methyl Acetate

(46) ##STR00041##

(47) A geometric isomer mixture of E:Z=57:43 of [3-(2-acetoxy-1-methylethylidene)-2,2-dimethylcyclobutyl]methyl acetate (1.78 g, 6.99 mmol) obtained in Example 3, methylene chloride (30 g) and a 30% solution of hydrogen bromide in acetic acid (2.83 g, 10.5 mmol) were placed in a reactor in a nitrogen atmosphere and stirred at 20° C. for 6 hours. Subsequently, a saturated aqueous solution of sodium bicarbonate was added to the reaction mixture, and the organic layer was separated and subjected to post-treatment by ordinary washing, drying, and concentration. Then, the obtained concentrated liquid was purified by silica gel column chromatography (hexane:ethyl acetate=30:1) to obtain the target 6 compound, [2,2-dimethyl-3-(2-bromo-1-methylethylidene)cyclobutyl]methyl acetate, as a geometric isomer mixture at E:Z=57:43 (1.70 g, 6.18 nmol) in a yield of 88%.

(48) The following is spectrum data of [2,2-dimethyl-3-(2-bromo-1-methylethylidene)cyclobutyl]methyl acetate (colorless or pale yellow oily liquid) thus produced.

(49) .sup.1H-NMR (500 MHz CDCl.sub.3): δ=1.15, 1.20 (3H, s, s), 1.26, 1.31 (3H, s, s), 1.59-1.60, 1.70-171 (3H, m), 2.03 (3H, s), 2.15-2.29 (2H, m), 2.60-2.75 (1H, m), 3.82, 3.94, 3.97 (2H, s, d, J=9.6 Hz, d, J 9.6 Hz), 4.08-4.15 (2H, m) ppm.

Example 8

Preparation of (3-isopropenyl-2,2-dimethylcyclobutyl)methyl acetate and (3-isopropylidene-2,2-dimethylcyclobutyl)methylacetate

(50) ##STR00042##

(51) A geometric isomer mixture of E:Z=57:43 of [3-(2-acetoxy-1-methylethylidene)-2,2-dimethylcyclobutyl]methyl acetate (483 mg, 1.90 mmol) obtained in Example 3, acetonitrile (12 g), 2-(di-tert-butylphosphino)biphenyl (230 mg, 0.771 mmol), and palladium acetate (40 mg, 0.18 mmol) were placed in a reactor in a nitrogen atmosphere and stirred at 20° C. Then, triethylamine (770 mg, 7.61 mmol) and formic acid (260 mg, 5.65 mmol) were added to form triethylammonium formate in the reaction system, and stirred at 30° C. for 19 hours. Subsequently, water was added to the reaction mixture, and the organic layer was separated and subjected to post-treatment by ordinary washing, drying and concentration. Then, the obtained concentrated liquid was purified by silica gel column chromatography (hexane:ethyl acetate=50:1) to obtain the target compounds, (3-isopropenyl-2,2-dimethylcyclobutyl)methyl acetate and (3-isopropylidene-2,2-dimethylcyclobutyl)methyl acetate, as a mixture of 78:18:4 of the cis form, the trans form and the regioisomer at the double bond (i.e., (3-isopropylidene-2,2-dimethylcyclobutyl)methyl acetate), (328 mg, 1.67 mmol) in a yield of 88%.

(52) The following is spectrum data of cis-(3-isopropenyl-2,2-dimethylcyclobutyl)methyl acetate (colorless or pale yellow oily 16 liquid) thus produced.

(53) IR (D-ATR): νmax=3080, 2957, 2870, 1743, 1647, 1460, 1385, 1368, 1240, 1162, 1031, 972, 886, 641, 607, 556 cm.sup.−1.

(54) .sup.1H-NMR (500 MHz CDCl.sub.3): δ=0.81 (3H, s), 1.19 (3H, s), 1.59 (1H, q, J=10.7 Hz) 1.64 (3H, t, J=0.8 Hz), 1.89 (1H, dt, J=7.6, 10.7 Hz), 2.02 (3H, s), 2.13-2.22 (1H, m), 2.37-2.41 (1H, m) 3.94 (1H, dd, J=8.6, 11.3 Hz); 4.04 (1H, dd, J=6.3, 11.3 Hz); 4.56 (1H, brs); 4.79-4.82 (1H, m) ppm.

(55) .sup.13C-NMR (150 MHz, CDCl.sub.3): δ=16.07, 21.02, 22.92, 22.96, 30.92, 39.74, 41.05, 48.83, 64.95, 109.42, 144.93, 171.05 ppm.

Example 9

Preparation of (3-isopropenyl-2,2-dimethylcyclobutyl)methyl Acetate and (3-isopropylidene-2,2-dimethylcyclobutyl)methyl Acetate

(56) ##STR00043##

(57) A geometric isomer mixture of E:Z 57:43 of [3-(2-acetoxy-1-methylethylidene)-2,2-dimethylcyclobutyl]methyl acetate (483 mg, 1.90 mmol) obtained in Example 3, acetonitrile (12 g), triphenylphosphine (200 mg, 0.763 mmol), and palladium acetate (40 mg, 0.18 mmol) were placed in a reactor in a nitrogen atmosphere and stirred at 20° C. Then, triethylamine (770 mg, 7.61 mmol) and formic acid (260 mg, 5.65 mmol) were added to form triethylammonium formate in the reaction system, and stirred under reflux for 24 hours. Subsequently, water was added to the reaction mixture, and the organic layer was separated and subjected to post-treatment by ordinary washing, drying and concentration. Then, the obtained concentrated liquid was purified by silica gel column chromatography (hexane:ethyl acetate=50:1) to obtain the target compounds, (3-isopropenyl-2,2-dimethylcyclobutyl)methyl acetate and (3-isopropylidene-2,2-dimethylcyclobutyl)ethyl acetate, as a mixture of 68:30:2 of the cis form, the trans form, and the regioisomer at the double bond (i.e., (3-isopropylidene-2,2-dimethylcyclobutyl)methyl acetate), (321 mg, 1.63 mmol) in a yield of 86%.

Example 10

Preparation of (3-isopropenyl-2,2-dimethylcyclobutyl)methyl Acetate and (3-isopropylidene-2,2-dimethylcyclobutyl)methylacetate

(58) ##STR00044##

(59) A geometric isomer mixture of E:Z=57:43 of [3-(2-acetoxy-1-methylethylidene)-2,2-dimethylcyclobutyl]methyl acetate (1.86 g, 7.33 mmol) obtained in Example 3, tetrahydrofuran (THF) (19 g), trioctylphosphine (220 mg, 0.594 nmol), and palladium acetate (33 mg, 0.15 mmol) were placed in a reactor in a nitrogen atmosphere and stirred at 20° C. Then, triethylamine (2.97 g, 29.3 mmol) and formic acid (1.01 g, 22.0 mmol) were added to form triethylammonium formate in the reaction system, and stirred at 35° C. for 5 hours. Subsequently, water was added to the reaction mixture, and the organic layer was separated and subjected to post-treatment by ordinary washing, drying and concentration. Then, the obtained concentrated liquid was purified by silica gel column chromatography (hexane:ethyl acetate=50:1) to obtain the target compounds, (3-isopropenyl-2,2-dimethylcyclobutyl)methyl acetate and (3-isopropylidene-2,2-dimethylcyclobutyl)methy acetate, as a mixture of 65:34:1 of the cis form, the trans form, and the regioisomer at the double bond (i.e., (3-isopropylidene-2,2-dimethylcyclobutyl)methyl acetate), (1.27 g, 6.45 mmol) in a yield of 88%.

Example 11

Preparation of (3-isopropenyl-2,2-dimethylcyclobutyl)methyl acetate and (3-isopropylidene-2,2-dimethylcyclobutyl)methylacetate

(60) ##STR00045##

(61) Palladium acetate (1.86 g, 8.27 mmol), tetrahydrofuran (THF) (1602 g), trioctylphosphine (12.3 g, 33.1 mmol), and [3-(2-acetoxy-1-methylethylidene)-2,2-dimethylcyclobutyl]methyl acetate as a geometric isomer mixture at E:Z=70:30 (420 g, 1.65 mol) were placed in a reactor in a nitrogen atmosphere and stirred at 45° C. Subsequently, a solution of triethylamine (335 g, 3.31 mol) and formic acid (114 g, 2.48 mol) in acetonitrile (MeCN) (335 g) was added dropwise at internal temperature in the reactor of 50° C. or below. After the completion of the dropwise addition, the mixture was stirred at 45° C. for 4 hours. Then, acetic acid and brine were added to the reaction mixture, and the organic layer was separated and subjected to post-treatment by ordinary washing, drying and concentration. Then, the obtained concentrated liquid was subjected to distillation at a reduced pressure to obtain the target compounds, (3-isopropenyl-2,2-dimethylcyclobutyl)methyl acetate and (3-isopropylidene-2,2-dimethylcyclobutyl)methyl acetate, as a mixture of 68:31:1 of the cis form, the trans form, and the regioisomer at the double bond (i.e., (3-isopropylidene-2,2-dimethylcyclobutyl)methyl acetate), (310 g, 1.58 mmol) in a yield of 96%. The spectrum data of cis-(3-isopropenyl-2,2-dimethylcyclobutyl)methyl acetate thus obtained (colorless or pale yellow oily liquid) had the same spectra as in Example 8.

Example 12

Preparation of (3-isopropenyl-2,2-dimethylcyclobutyl)methyl 2-methylbutanoate and (3-isopropylidene-2,2-dimethylcyclobutyl)methyl 2-methylbutanoate

(62) ##STR00046##

(63) A geometric isomer mixture of E:Z 57:43 of (3-[2-(2-methylbutanoyloxy)-1-methylethylidene]-2,2-dimethylcyclobutyl)methyl 2-methylbutanoate (1.84 g, 5.43 mmol) obtained in Example 4, tetrahydrofuran (THF) (40 g), trioctylphosphine (160 mg, 0.436 mmol), and palladium acetate (24 mg, 0.11 mmol) were placed in a reactor in a nitrogen atmosphere and stirred at 20° C. for 1 hour. Then, triethylamine (2.19 g, 21.7 nmol) and formic acid (750 mg, 16.3 mmol) were added to form triethylammonium formate in the reaction system, and stirred at 35° C. for 24 hours. Subsequently, water was added to the reaction mixture, and the organic layer was separated and subjected to post-treatment by ordinary washing drying and concentration. Then, the obtained concentrated liquid was purified by silica gel column chromatography (hexane:ethyl acetate 80:1) to obtain the target compounds, (3-isopropenyl-2,2-dimethylcyclobutyl)methyl 2-methylbutanoate and (3-isopropylidene-2,2-dimethylcyclobutyl)methyl 2-methylbutanoate, as a mixture of 64:32:4 of the cis form, the trans form, and the regioisomer at the double bond (i.e., (3-isopropylidene-2,2-dimethylcyclobutyl)methyl 2-methylbutanoate), (1.15 g, 4.84 mmol) in a yield of 89%.

(64) The following is spectrum data of cis-(3-isopropenyl-2,2-dimethylcyclobutyl)methyl 2-methylbutanoate (colorless or pale yellow oily liquid) thus produced.

(65) .sup.1H-NMR (500 MHz CDCl.sub.3): δ=0.81 (3H, s), 0.89 (3H, t, J=7.5 Hz), 1.11 (3H, q, J=7.0 Hz), 1.20 (3H, s), 1.40-1.51 (1H, m), 1.56-1.72 (5H, m), 1.87 (1H, dt, J=7.6, 10.7 Hz), 2.13-2.22 (1H, m), 2.29-2.41 (2H, m), 3.92, 3.94 (1H, dd, J=6.1, 11.1 Hz, dd, J=6.1, 11.1 Hz, 4.04, 4.05 (1H, dd, J=6.1, 11.1 Hz, dd, J=6.1, 11.1 Hz), 4.55 (1H, brs), 4.78-4.81 (1H, m) ppm.

Example 13

Preparation of 1-chloromethyl-3-isopropenyl-2,2-dimethylcyclobutane and 1-chloromethyl-3-isopropylidene-2,2-dimethylcyclobutane

(66) ##STR00047##

(67) A geometric isomer mixture of E:Z=57:43 of 1-chloromethyl-3-(2-chloro-1-methylethylidene)-2,2-dimethylcyclobutane (988 mg, 4.77 mol) obtained in Example 5, tetrahydrofuran (THF) (20 g), trioctylphosphine (280 mg, 0.763 mmol), and palladium acetate (40 mg, 0.18 mmol) were placed in a reactor in a nitrogen atmosphere and stirred at 20° C. for 1 hour. Then, triethylamine (1.93 g, 19.1 nmol) and formic acid (660 mg, 14.3 mmol) were added to form triethylammonium formate in the reaction system, and stirred at 55° C. for 24 hours. Subsequently, water was added to the reaction mixture, and the organic layer was separated and subjected to post-treatment by ordinary washing, drying and concentration. Then, the obtained concentrated liquid was purified by silica gel column chromatography (hexane) to obtain the target compounds, 1-chloromethyl-3-isopropenyl-2,2-dimethylcyclobutane and 1-chloromethyl-3-isopropylidene-2,2-dimethylyclobutane, as a mixture of 53:46:1 of the cis form, the trans form, and the regioisomer at the double bond (i.e., 1-chloromethyl-3-isopropylidene-2,2-dimethylcyclobutane), (553 mg, 3.20 mmol) in a yield of 67%.

(68) The following is spectrum data of 1-chloromethyl-3-isopropenyl-2,2-dimethylyclobutane (colorless or pale yellow oily liquid) thus produced.

(69) .sup.1H-NMR (500 MHz CDCl.sub.3): δ=0.85, 0.98 (3H, s), 1.14, 1.26 (3H, s), 1.57, 1.72 (1H, q, J=10.7 Hz, m), 1.66-1.67 (3H, m), 1.98, 2.04-2.10 (1H, dt, J=7.7, 10.7 Hz, m), 2.15-2.30 (1H, m), 2.35-2.39, 2.52-2.57 (1H, m), 3.40-3.49, 3.60, 3.72 (2H, m, dd, J=8.8, 10.7 Hz, dd, J=6.8, 10.7 Hz), 4.56, 4.66 (1H, brs, brs), 4.80-4.83, 4.85-4.87 (1H, m) ppm.

Example 14

Preparation of (3-isopropenyl-2,2-dimethylcyclobutyl)methanol

(70) ##STR00048##

(71) The target crude product, [2-(3-Hydroxymethyl-2,2-dimethylcyclobutylidene)propyl]triphenylphosphonium bromide, (872 mg, 1.76 mmol) obtained in Example 6 and tetrahydrofuran (THF) (70 g) were placed in a reactor in a nitrogen atmosphere and stirred at 0° C. Subsequently, a solution of 3.60 M sodium bis(2-methoxyethoxy) aluminum hydride (2.00 ml, 7.20 mmol) in toluene was added dropwise at internal temperature in the reactor of 10° C. or below. After the completion of the dropwise addition, the mixture was heated gradually up to 20° C. with stirring for 1 hour. Subsequently, a 10% by weight solution of sodium hydroxide in water was added to the reaction mixture, and the organic layer was separated and subjected to post-treatment by ordinary washing, drying and concentration. Then, the obtained concentrated liquid was purified by silica gel column chromatography (hexane:ethyl acetate=10:1) to obtain the target compound, (3-isopropenyl-2,2-dimethylcyclobutyl)methanol, as a geometric isomer mixture at 77:23 of the cis form and the trans form, (195 mg, 1.27 mmol) in a yield of 72%. Double bond regioisomer, (3-isopropylidene-2,2-dimethylcyclobutyl)methanol was not detected in GC.

(72) The following is spectrum data of cis-(3-isopropenyl-2,2-dimethylcyclobutyl)methanol (colorless or pale yellow oily liquid) thus produced.

(73) .sup.1H-NMR (500 MHz CDCl.sub.3): δ=0.82 (3H, s), 1.22 (3H, s), 1.55 (1H, q, J=10.7 Hz), 1.65 (3H, s), 1.85-1.91 (1H, m), 2.03-2.10 (1H, m), 2.34-2.39 (1H, m), 3.52 (1H, dd, J=6.5, 10.7 Hz), 3.59 (1H, dd, J=8.3, 10.7 Hz), 4.55 (1H, brs), 4.78-4.81 (1H, m) ppm.

(74) The following is spectrum data of trans-(3-isopropenyl-2,2-dimethylcyclobutyl)methanol (colorless or pale yellow oily liquid) thus produced.

(75) .sup.1H-NMR (500 MHz CDCl.sub.3): δ=0.95 (3H, s), 1.12 (3H, s), 1.51 (1H, brs), 1.58-1.63 (1H, m), 1.65 (3H, s), 1.76-1.90 (1H, m), 2.03-2.14 (1H, m), 2.53-2.59 (1H, m), 3.69 (1H, dd, J=7.6, 10.7 Hz), 3.85 (1H, dd, J=7.3, 10.7 Hz), 4.62 (1H, brs), 4.81-4.84 (1H, m) ppm.

Example 15

Preparation of (3-isopropylidene-2,2-dimethylcyclobutyl)methanol

(76) ##STR00049##

(77) Lithium aluminum hydride (570 mg, 15.0 mmol) and tetrahydrofuran (THF) (60 g) were placed in a reactor in a nitrogen atmosphere and stirred at 0° C. for 1 hour. A geometric isomer mixture of E:Z=57:43 of [2,2-dimethyl-3-(2-bromo-1-methylethylidene)cyclobutyl]methyl acetate (1.62 g, 5.89 mmol) was added dropwise to this solution at internal temperature in the reactor of 5° C. or below. After the completion of the dropwise addition, the mixture was heated gradually up to 20° C. for 6 hour with stirring. Subsequently, water (570 mg) and a 15% by weight solution of sodium hydroxide (570 mg) were added, followed by further addition of water (1.71 g), and filtration. The obtained filtrate was concentrated at a reduced pressure, and purified by silica gel column chromatography (hexane:ethyl acetate=10:1) to obtain the target compound, (3-isopropylidene-2,2-dimethylcyclobutyl)methanol (909 mg, 5.89 mmol) in a yield of 100%.

(78) Double bond regioisomer, (3-isopropenyl-2,2-dimethylcyclobutyl)methanol was not detected in GC.

(79) The following is spectrum data of (3-isopropylidene-2,2-dimethylcyclobutyl)methanol (colorless or pale yellow oily liquid) thus produced.

(80) .sup.1H-NMR (500 MHz CDCl.sub.3): δ=1.15 (3H, s), 1.26 (3H, s), 1.45 (3H, s), 1.56-1.58 (3H, m), 1.63 (1H, brs), 2.03-2.14 (2H, m), 2.54-2.62 (1H, m), 3.61 (1H, dd, J=6.9, 10.7 Hz), 3.76 (1H, dd, J=7.7, 10.7 Hz) ppm.

(81) .sup.13C-NMR (150 MHz, CDCl.sub.3): δ=18.48, 19.53, 20.90, 27.70, 28.67, 42.65, 44.05, 64.30, 122.42, 137.39 ppm.

Example 16

Preparation of (3-isopropenyl-2,2-dimethylcyclobutyl)methyl acetate and (3-isopropylidene-2,2-dimethylcyclobutyl)methylacetate

(82) ##STR00050##

(83) A mixture of 1-chloromethyl-3-isopropenyl-2,2-dimethylcyclobutane and 1-chloromethyl-3-isopropylidene-2,2-dimethylcyclobutane (535 mg, 3.10 mmol) obtained as in Example 13, sodium acetate (580 mg, 7.07 mmol), sodium iodide (100 mg, 0.667 mmol), and N,N-dimethylacetamide (20 g) were placed in a reactor in a nitrogen atmosphere and stirred at 150° C. for 24 hours. Subsequently, water was added to the reaction mixture, and the organic layer was separated and subjected to post-treatment by ordinary washing, drying and concentration. Then, the obtained concentrated liquid was purified by silica gel column chromatography (hexane:ethyl acetate:=50:1) to obtain the target compounds, (3-isopropenyl-2,2-dimethylcyclobutyl)methyl acetate and (3-isopropylidene-2,2-dimethylcyclobutyl)methyl acetate, as a mixture of 57:42:1 of the cis form, the trans form, and the regioisomer at the double bond (i.e., (3-isopropylidene-2,2-dimethylcyclobutyl)methyl acetate), (255 mg, 1.30 mmol) in a yield of 42%.

Example 17

Preparation of (3-isopropenyl-2,2-dimethylcyclobutyl)methyl acetate

(84) ##STR00051##

(85) A geometric isomer mixture of 77:23 of the cis form and the trans form of (3-isopropenyl-2,2-dimethylcyclobutyl)methano obtained as in Example 14 (154 mg, 1.00 mmol), pyridine (316 mg) and toluene (10 g) were placed in a reactor in a nitrogen atmosphere and stirred at 0° C. Subsequently, acetic anhydride (204 mg, 2.00 mmol) was added dropwise at internal temperature in the reactor of 10° C. or below. After the completion of the dropwise addition, the mixture was heated gradually up to 20° C. for 6 hours with stirring. Subsequently, water was added to the reaction mixture, and the organic layer was separated and subjected to post-treatment by ordinary washing, drying and concentration. Then, the obtained concentrated liquid was purified by silica gel column chromatography (hexane:ethyl acetate=50:1) to obtain the target compound, (3-isopropenyl-2,2-dimethylcyclobutyl)methyl acetate, as a geometric isomer mixture at 77:23 of the cis form and the trans form, (183 mg, 0.930 mmol) in a yield of 93%.

Example 18

Preparation of (3-isopropylidene-2,2-dimethylcyclobutyl)methyl Acetate

(86) ##STR00052##

(87) (3-isopropylidene-2,2-dimethylcyclobutyl)methanol (818 mg, 5.30 mmol) obtained as in Example 15, toluene (10 g), pyridine (1.68 g, 21.2 mmol) and acetic anhydride (1.09 g, 10.7 mmol) were placed in a reactor in a nitrogen atmosphere and stirred at 20° C. for 24 hours. Subsequently, water was added to the reaction mixture, and the organic layer was separated and subjected to post-treatment by ordinary washing, drying and concentration. Then, the obtained concentrated liquid was purified by silica gel column chromatography (hexane:ethyl acetate 50:1) to obtain the target compound, (3-isopropylidene-2,2-dimethylcyclobutyl)methyl acetate, (911 mg, 4.64 mmol) in a yield of 88%.

(88) The following is spectrum data of (3-isopropylidene-2,2-dimethylcyclobutyl)methyl acetate (colorless or pale yellow oily liquid) thus produced.

(89) .sup.1H-NMR (500 MHz CDCl.sub.3): δ=1.13 (3H, s), 1.24 (3H, s), 1.45 (3H, s), 1.57 (3H, t, J=1.9 Hz), 2.03 (3H, s), 2.10-2.22 (2H, m), 2.56-2.63 (1H, m), 4.07-4.15 (2H, m) ppm.

(90) .sup.13C-NMR (150 MHz, CDCl.sub.3): δ=18.49, 19.53, 20.98, 21.00, 27.72, 28.37, 38.99, 44.20, 65.73, 122.67, 136.93, 171.20 ppm.

Example 19

Preparation of (3-isopropylidene-2,2-dimethylcyclobutyl)methyl methanesulfonate

(91) ##STR00053##

(92) (3-Isopropylidene-2,2-dimethylcyclobutyl)methanol (858 mg, 5.56 mmol) obtained according to Example 15, tetrahydrofuran (THF) (20 g), and triethylamine (1.71 g, 16.9 mmol) were placed in a reactor in a nitrogen atmosphere and stirred at 0° C. for 1 hour. Methanesulfonyl chloride (1.09 g, 10.7 mmol) was added dropwise to this solution at internal temperature in the reactor of 10° C. or below. After the completion of the dropwise addition, the mixture was stirred at 20° C. for 1 hour. Subsequently, water was added to the reaction mixture, and the organic layer was separated and subjected to post-treatment by ordinary washing, drying and concentration. Then, the obtained concentrated liquid was purified by silica gel column chromatography (hexane:ethyl acetate=10:1) to obtain the target compound, (3-isopropylidene-2,2-dimethylcyclobutyl)methyl methanesulfonate, (1.29 g, 5.56 mol) in a yield of 100%.

(93) The following is spectrum data of (3-isopropylidene-2,2-dimethylcyclobutyl)methyl methanesulfonate (colorless or pale yellow oily liquid) thus produced.

(94) .sup.1H-NMR (500 MHz CDCl.sub.3): δ=1.17 (3H, s), 1.27 (3H, s), 1.45 (3H, brs), 1.58 (3H, t, J 1.9 Hz), 2.15-2.22 (1H, m), 2.25-2.33 (1H, m), 2.61-2.67 (1H, m), 3.00 (3H, s), 4.23 (1H, dd, J=7.3, 9.9 Hz), 4.31 (1H, dd, J=8.0, 10.01 Hz) ppm.

Example 20

Preparation of (3-isopropylidene-2,2-dimethylcyclobutyl)methyl 3-methyl-2-butenoate

(95) ##STR00054##

(96) (3-Isopropylidene-2,2-dimethylcyclobutyl)methyl methanesulfonate (1.29 g, 5.56 mmol) obtained as in Example 19, toluene (40 g), water (430 mg), senecioic acid (3-methyl-2-butenoic acid) (690 mg, 6.92 mmol), potassium carbonate (610 mg, 4.39 mmol), and tetrabutylammonium chloride (60 mg, 0.23 mmol) were placed in a reactor in a nitrogen atmosphere and stirred at 100° C. for 24 hours. Subsequently, water was added to the reaction mixture, and the organic layer was separated and subjected to post-treatment by ordinary washing, drying and concentration. Then, the obtained concentrated liquid was purified by silica gel column chromatography (hexane:ethyl acetate=50:1) to obtain the target compound, (3-isopropylidene-2,2-dimethylcyclobutyl)methyl 3-methyl-2-butenoate, (1.20 g, 5.06 mmol) in a yield of 91%.

(97) The following is spectrum data of (3-isopropylidene-2,2-dimethylcyclobutyl)methyl 3-methyl-2-butenoate (colorless or pale yellow oily liquid) thus produced.

(98) IR (D-ATR): νmax=2956, 2917, 2864, 1719, 1659, 1449, 1376, 1361, 1349, 1272, 1227, 1146, 1076, 993, 851 cm.sup.−1.

(99) .sup.1H-NMR (500 MHz, CDCl.sub.3): δ=1.14 (3H, s), 1.25 (3H, s), 1.45 (3H, brs), 1.56-1.58 (3H, m), 1.88 (3H, d, J=1.5 Hz), 2.12-2.30 (5H, m), 2.56-2.64 (1H, m), 4.11 (1H, dd, J=6.8, 11.4 Hz), 4.15 (1H, dd, J=8.0, 11.5 Hz), 5.64-5.66 (1H, m) ppm.

(100) .sup.13C-NMR (150 MHz, CDCl.sub.3): δ=18.50, 19.54, 20.15, 20.99, 27.34, 27.78, 28.39, 39.14, 44.21, 64.75, 116.15, 122.53, 137.18, 156.25, 166.82 ppm.

Example 21

Preparation of (3-isopropenyl-2,2-dimethylcyclobutyl)methanol and (3-isopropylidene-2,2-dimethylcyclobutyl)methanol

(101) ##STR00055##

(102) A geometric isomer mixture of (3-isopropenyl-2,2-dimethylcyclobutyl)methyl acetate (60.3 g, 307 mmol) obtained as in Example 11, methanol (94 g), and a 25% aqueous solution of sodium hydroxide (94 g) were placed in a reactor in a nitrogen atmosphere and stirred at 20° C. for 12 hours. Subsequently, brine was added to the reaction mixture, and the organic layer was separated and subjected to post-treatment by ordinary washing, drying and concentration. Then, the obtained concentrated liquid was subjected to distillation at a reduced pressure to obtain the target compounds, (3-isopropenyl-2,2-dimethylcyclobutyl)methanol and (3-isopropylidene-2,2-dimethylcyclobutyl)methanol, as a mixture of 67:32:1 of the cis form, the trans form, and the regioisomer at the double bond (i.e., (3-isopropylidene-2,2-dimethylcyclobutyl)methanol), (46.0 g, 298 mmol) in a yield of 97%. The spectra data of cis-(3-isopropenyl-2,2-dimethylcyclobutyl)methanol thus obtained (colorless or pale yellow oily liquid) and trans-(3-isopropenyl-2,2-dimethylcyclobutyl)methanol thus obtained (colorless or pale yellow oily liquid) had the same spectra as in Example 14.

Example 22

Preparation of (3-isopropenyl-2,2-dimethylcyclobutyl)methyl 2-methylbutanoate and (3-isopropylidene-2,2-dimethylcyclobutyl)methyl 2-methylbutanoate

(103) ##STR00056##

(104) A geometric isomer mixture of (3-isopropenyl-2,2-dimethylcyclobutyl)methanol (12.6 g, 82.0 mmol) obtained as in Example 21, tetrahydrofuran (TH) (100 g), and pyridine (16.9 g, 213 mmol) were placed in a reactor in a nitrogen atmosphere and stirred at 0° C. Subsequently, 2-methylbutanoyl chloride (12.9 g, 107 mmol) was added dropwise to the solution at internal temperature in the reactor of 15° C. or below. After the completion of the dropwise addition, the mixture was heated gradually up to 20° C. for 6 hours with stirring. Subsequently, brine was added to the reaction mixture, and the organic layer 16 was separated and subjected to post-treatment by ordinary washing, drying and concentration. Then, the obtained concentrated liquid was subjected to distillation at a reduced pressure to obtain the target compounds, (3-isopropenyl-2,2-dimethylcyclobutyl)methyl 2-methylbutanoate and (3-isopropylidene-2,2-dimethylcyclobutyl)methyl 2-methylbutanoate, as a mixture of 68:31:1 of the cis form, the trans form, and the regioisomer at the double bond (i.e., (3-isopropylidene-2,2-dimethylcyclobutyl)methyl 2-methylbutanoate), (19.5 g, 81.6 mmol) in a yield of 100%. The spectra data of cis-(3-isopropenyl-2,2-dimethylcyclobutyl)methyl 2-methylbutanoate thus obtained ad the same spectra as in Example 14.

Example 23

Preparation of (3-isopropenyl-2,2-dimethylcyclobutyl)methyl 3-methyl-3-butenoate and (3-isopropylidene-2,2-dimethylcyclobutyl)methyl 3-methyl-3-butenoate

(105) ##STR00057##

(106) A geometric isomer mixture of (3-isopropenyl-2,2-dimethylcyclobutyl)methanol (13.4 g, 86.6 mmol) obtained as in Example 21, dichloromethane (665 g), 3-methyl-3-butenoic acid (12.5 g, 125 mmol), and 4-dimethylaminopyridine (DMAP)(1.06 g, 8.66 mmol) were placed in a reactor in a nitrogen atmosphere and stirred at 0° C. N,N′-dicyclohexylcarbodiimide (DCC) (24.8 g, 120 mmol) was added. The mixture was heated gradually up to 20° C. for 2 hours with stirring. Subsequently, ether and brine were added to the reaction mixture, and the organic layer was separated and subjected to post-treatment by ordinary washing, drying and concentration. Then, the obtained concentrated liquid was purified by silica gel column chromatography (hexane:ethyl acetate=40:1) to obtain the target compounds, (3-isopropenyl-2,2-dimethylcyclobutyl)methyl 3-methyl-3-butenoate and (3-isopropylidene-2,2-dimethylcyclobutyl)methyl 3-methyl-3-butenoate, as a mixture of 67:32:1 of the cis form, the trans form, and the regioisomer at the double bond (i.e., (3-isopropylidene-2,2-dimethylcyclobutyl)methyl 3-methyl-3-butenoate), (20.2 g, 85.6 nmol) in a yield of 99%.

(107) The following is spectrum data of cis-(3-isopropenyl-2,2-dimethylcyclobutyl)methyl 3-methyl-3-butenoate (colorless or pale yellow oily liquid) thus produced.

(108) IR (D-ATR): νmax=3080, 2956, 2870, 1738, 1648, 1454, 1385, 1370, 1337, 1284, 1241, 1153, 1075, 1030, 994, 889 cm-1.

(109) .sup.1H-NMR (500 MHz CDCl.sub.3): δ=0.80 (3H, s), 1.19 (3H, s), 1.61 (1H, q, J 10.7 Hz), 1.64-1.65 (3H, m), 1.79-1.81 (3H, m), 1.88 (1H, dt, J=10.7, 7.5 Hz), 2.15-2.22 (1H, m), 2.39 (1H, dd, J=10.7, 7.5 Hz), 3.00-3.01 (2H, m), 3.96 (1H, dd, J=8.8, 11.1 Hz), 4.07 (1H, dd), J=6.5, 11.1 Hz), 4.56 (1H, s), 4.79-4.81 (1H, m), 4.83-4.84 (1H, m), 4.89-4.91 (1H, m) ppm.

(110) .sup.13C-NMR (150 MHz, CDCl.sub.3): δ=16.09, 22.46, 22.86, 22.94, 30.91, 39.78, 41.07, 43.57, 48.81, 65.12, 109.44, 114.61, 138.52, 144.94, 171.32, ppm.

Example 24

Preparation of (3-isopropylidene-2,2-dimethylcyclobutyl)methyl 2-methylbutanoate

(111) ##STR00058##

(112) (3-Isopropylidene-2,2-dimethylcyclobutyl)methanol (9.16 g, 59.4 mmol) obtained according to Example 15, tetrahydrofuran (THF) (100 g), and pyridine (14.1 g) were placed in a reactor in a nitrogen atmosphere and stirred at 0° C. 2-Methylbutanoyl chloride (10.8 g, 89.2 mmol) was added dropwise at an internal temperature in the reactor of 15° C. or below. After the completion of the dropwise addition, the mixture was heated gradually up to 20° C. for 3 hours with stirring. Subsequently, brine was added to the reaction mixture, and the organic layer was separated and subjected to post-treatment by ordinary washing, drying and concentration. Then, the obtained concentrated liquid was subjected to distillation at a reduced pressure to obtain the target compound, (3-isopropylidene-2,2-dimethylcyclobutyl)methyl 2-methylbutanoate, (14.2 g, 59.4 mmol) in a yield of 100%.

(113) The following is spectrum data of (3-isopropylidene-2,2-dimethylcyclobutyl)methyl 2-methylbutanoate (colorless or pale yellow oily liquid) thus produced.

(114) IR (D-ATR): νmax 2964, 2935, 2878, 1735, 1461, 1383, 1361, 1264, 1240, 1186, 1152, 1081, 1013, 973, 889, 755 cm.sup.−1.

(115) .sup.1H-NMR (500 MHz CDCl.sub.3): δ 0.89 (3H, t, J=7.5 Hz), 1.13 (3H, d, J:=8.0 Hz), 1.13 (3H, s), 1.24 (3H, s), 1.42-1.50 (4H, m), 1.57 (3H, t, J=1.7 Hz). 1.60-1.77 (1H, m), 2.09-2.23 (2H, m), 2.30-2.39 (1H, m), 2.55-2.61 (1H, m), 4.08-4.15 (2H, m) ppm.

(116) .sup.13C-NMR (150 MHz, CDCl.sub.3): δ=11.64, 16.58, 16.63, 18.50, 19.54, 21.02, 21.04, 26.72, 26.75, 27.50, 27.52, 28.40, 39.12, 39.15, 41.17, 44.20, 65.33, 122.60, 136.99, 176.73 ppm.