Method for producing lactam compound, and lactam compound produced thereby

Abstract

The present invention relates to a method for producing a lactam compound from dioxazolone in the presence of a catalyst having a particular ligand, and to a lactam compound produced thereby, and can produce a lactam compound with excellent selectivity and an excellent yield by using the combination of a starting material having a particular functional group and a particular catalyst having a particular ligand.

Claims

1. A method of preparing a lactam compound, the method comprising: amidating a 3-substituted dioxazol-one compound in the presence of a catalyst represented by the following Chemical Formula 1 and a base to prepare a lactam compound: ##STR00086## wherein M is iridium, rhodium, ruthenium, or cobalt; X is a halogen; R1 to R5 are independently of one another hydrogen or (C1-C7)alkyl; and R6 is a halogen, (C1-C20)alkyl, halo(C1-C20)alkyl, (C1-C20)alkoxy, (C6-C20)aryl, or (C3-C20)heteroaryl; and n is an integer of 0 to 6.

2. The method of preparing a lactam compound of claim 1, wherein amidating a 3-substituted dioxazol-one compound of the following Chemical Formula 2 in the presence of the catalyst represented by Chemical Formula 1 and the base to prepare a lactam compound of the following Chemical Formula 3 is included: ##STR00087## wherein Ra1 and Ra2 are independently of each other hydrogen, (C1-C20)alkyl, (C6-C20)aryl, or (C3-C20)heterocyclalkyl; Ra3 to Ra6 are independently of one another hydrogen, a halogen, (C1-C20)alkyl, halo(C1-C20)alkyl, (C2-C20)alkenyl, (C2-C20)alkynyl, (C1-C20)alkoxy, (C6-C20)aryl, or (C3-C20)heteroaryl, or may be connected to an adjacent substituent to form an aromatic ring or an alicyclic ring with or without a fused ring; and q is an integer of 1 or 2.

3. The method of preparing a lactam compound of claim 1, wherein amidating a 3-substituted dioxazol-one compound of the following Chemical Formula 4 in the presence of the catalyst represented by Chemical Formula 1 and the base to prepare a lactam compound of the following Chemical Formula 5 is included: ##STR00088## wherein Ra1 and Ra2 are independently of each other hydrogen, (C1-C20)alkyl, (C6-C20)aryl, or (C3-C20)heterocyclalkyl; Ra7 to Ra10) are independently of one another hydrogen, a halogen, (C1-C20)alkyl, halo(C1-C20)alkyl, (C2-C20)alkenyl, (C2-C20)alkynyl, (C1-C20)alkoxy, (C6-C20)aryl, or (C3-C20)heteroaryl, or may be connected to an adjacent substituent to form an aromatic ring or an alicyclic ring with or without a fused ring; q is an integer of 1 or 2.

4. The method of preparing a lactam compound of claim 1, wherein amidating a 3-substituted dioxazol-one compound of the following Chemical Formula 6 in the presence of the catalyst represented by Chemical Formula 1 and the base to prepare a lactam compound of the following Chemical Formula 7 is included: ##STR00089## wherein Ra1 and Ra2 are independently of each other hydrogen, (C1-C20)alkyl, (C6-C20)aryl, or (C3-C20)heterocycloalkyl; Ra7 to Ra11) are independently of one another hydrogen, a halogen, (C1-C20)alkyl, halo(C1-C20)alkyl, (C2-C20)alkenyl, (C2-C20)alkynyl, (C1-C20)alkoxy, (C6-C20)aryl, or (C3-C20)heteroaryl, or may be connected to an adjacent substituent to form an aromatic ring or an alicyclic ring with or without a fused ring; and q is an integer of 1 or 2.

5. The method of preparing a lactam compound of claim 1, wherein amidating a 3-substituted dioxazol-one compound of the following Chemical Formula 8 in the presence of the catalyst represented by Chemical Formula 1 and the base to prepare a lactam compound of the following Chemical Formula 9 is included: ##STR00090## wherein Ra11 to Ra14 are independently of one another hydrogen or (C1-C20)alkyl; Ra15 is a halogen, (C1-C20)alkyl, halo(C1-C20)alkyl, (C2-C20)alkenyl, (C2-C20)alkynyl, (C1-C20)alkoxy, (C6-C20)aryl, or (C3-C20)heteroaryl; Ra16 is hydrogen or (C1-C20)alkyl; and p is an integer of 0 to 4.

6. The method of preparing a lactam compound of claim 1, wherein the catalyst is used at 0.01 to 0.1 mol with respect to 1 mol of the 3-substituted dioxazol-one compound.

7. The method of preparing a lactam compound of claim 1, wherein the base is one or two or more selected from NaBArF4, AgSbF6, AgNTf2, AgBF4, AgPF6, AgOTf, and AgOAc.

8. The method of preparing a lactam compound of claim 1, wherein the base is used at 0.01 to 0.1 mol with respect to 1 mol of the 3-substituted dioxazol-one compound.

9. The method of preparing a lactam compound of claim 1, wherein the amidating is performed at 20 to 80° C.

10. The method of preparing a lactam compound of claim 1, wherein in Chemical Formula 1, M is iridium, X is chloro, R1 to R5 are independently of one another (C1-C30)alkyl, R6 is a halogen, and n is an integer of 0 to 2.

11. The method of preparing a lactam compound of claim 2, wherein Ra1 and Ra2 are independently of each other hydrogen, (C6-C20)aryl, or phthalimido; Ra3 to Ra6 are independently of one another hydrogen, a halogen, (C1-C20)alkyl, halo(C1-C20)alkyl, or (C1-C20)alkoxy, or may be connected to an adjacent substituent to form an aromatic ring with or without a fused ring; and q is an integer of 1 or 2.

12. The method of preparing a lactam compound of claim 3, wherein Ra1 and Ra2 are independently of each other hydrogen or phthalimido; Ra7 to Ra10 are independently of one another hydrogen, a halogen, (C1-C20)alkyl, or (C1-C20)alkoxy, or may be connected to an adjacent substituent to form an aromatic ring with or without a fused ring; and q is an integer of 1 or 2.

13. The method of preparing a lactam compound of claim 5, wherein Ra11 to Ra14 are independently of one another hydrogen; Ra15 is a halogen, (C1-C20)alkyl, or (C1-C20)alkoxy; Ra16 is hydrogen or (C1-C20)alkyl; and q is an integer of 0 or 1.

14. The method of preparing a lactam compound of claim 4, wherein Ra1 and Ra2 are independently of each other hydrogen or phthalimido; Ra7 to Ra10) are independently of one another hydrogen, a halogen, (C1-C20)alkyl, or (C1-C20)alkoxy, or may be connected to an adjacent substituent to form an aromatic ring with or without a fused ring; and q is an integer of 1 or 2.

Description

EXAMPLE 1: PREPARATION OF CATALYST

[Examples 1] Preparation of Catalyst A

(1) ##STR00013##

(2) [IrCp*Cl.sub.2].sub.2 (Cp*: pentamethylcyclopentadienyl) (0.20 g, 0.25 mmol), quinolin-8-ol (72.6 mg, 0.50 mmol), sodium carbonate (0.21 g, 2.0 mmol), and acetone (10 mL) were added to a vial and the mixture was stirred at room temperature for 12 hours. After the reaction was completed, the reactants were filtered with celite (dichloromethane (15 mL×3)), the solvent was removed by distillation under reduced pressure, and separation and purification were performed by column chromatography (n-hexane/acetone=2:1 to 1:1) to prepare Catalyst A.

8-Hydroxyquinoline Bound Cp*-Iridium Complex (Catalyst A)

(3) ##STR00014##
Orange solid (0.20 g, 80%); .sup.1H NMR (600 Hz, CDCl.sub.3) δ 8.54 (d, J=4.9 Hz, 1H), 8.03 (d, J=8.3 Hz, 1H), 7.36 (t, J=7.9 Hz, 1H), 7.30 (dd, J=8.3, 4.9 Hz, 1H), 7.00 (d, J=7.9 Hz, 1H), 6.78 (d, J=7.9 Hz, 1H), 1.73 (s, 15H); .sup.13C NMR (150 MHz, CDCl.sub.3) δ 169.1, 146.0, 145.8, 137.7, 131.0, 130.7, 121.9, 115.6, 110.9, 84.8 (Cp*), 8.9 (Cp*); IR (cm.sup.−1) 1564, 1455, 1367, 1320, 1111, 826, 751, 512; HRMS (EI) m/z calcd. for C.sub.19H.sub.21ClIrNO [M].sup.+: 507.0941. found: 507.0943.

[Examples 2] Preparation of Catalyst B

(4) Catalyst B was prepared in the same manner as in Example 1, except that 5,7-dichloroquinolin-8-ol (0.50 mmol) was used instead of quinolin-8-ol.

5,7-Dichloroquinolin-8-ol Bound Cp*-Iridium Complex (Catalyst B)

(5) ##STR00015##
Yellow solid (0.19 g, 67%); .sup.1H NMR (800 MHz, CD.sub.2Cl.sub.2) δ 8.62 (dd, J=5.0, 1.3 Hz, 1H), 8.37 (dd, J=8.6, 1.3 Hz, 1H), 7.57 (s, 1H), 7.50 (dd, J=8.6, 4.9 Hz, 1H), 1.69 (s, 15H); .sup.13C NMR (200 MHz, CD.sub.2Cl.sub.2) δ 164.5, 148.2, 146.7, 135.6, 130.5, 127.6, 123.5, 118.9, 113.1, 85.9, 9.1; IR (cm.sup.−1) 2920, 1441, 1368, 1193, 974, 745, 656; HRMS (EI) m/z calcd. for C.sub.19H.sub.19Cl.sub.3IrNO [M].sup.+: 575.0161. found: 575.0164.

[Comparative Example 1] Preparation of Catalyst C

(6) ##STR00016##

(7) [IrCp*Cl.sub.2].sub.2 (Cp*: pentamethylcyclopentadienyl) (0.4106 g, 0.5154 mmol), 2-(2′-pyridyl)-2-propanol (0.1420 g, 1.036 mmol), sodium bicarbonate (0.345 g, 4.11 mmol), and acetone (50 mL) were added to a vial and the mixture was stirred at room temperature for 2 hours. After the reaction was completed, the reactants were filtered with celite (dichloromethane (15 mL×3)), the solvent was removed by distillation under reduced pressure, and separation and purification were performed by column chromatography (n-hexane/acetone=2:1 to 1:1) to prepare Catalyst C.

2-(2′-Pyridyl)-2-Propanol Bound Cp*-Iridium Complex (Catalyst C)

(8) ##STR00017##
Yellow solid (0.416 g, 81%); .sup.1H NMR (400 MHz, MeOD) δ 8.69 (dt, J=5.2, 1.3 Hz, 1H), 7.88 (td, J=7.9, 1.5 Hz, 1H), 7.467.31 (m, 2H), 1.67 (s, 15H), 1.46 (s, 6H); .sup.13C NMR (150 MHz, MeOD) δ 177.34, 150.97, 139.53, 125.54, 122.95, 85.97, 84.74, 33.67, 9.01.

[Comparative Example 2] Preparation of Catalyst D

(9) ##STR00018##

(10) [IrCp*Cl.sub.2].sub.2 (Cp*: pentamethylcyclopentadienyl) (0.20 g, 0.25 mmol), 8-[N—(N,N-Dimethylaminocarbonyl)amino]quinoline (0.50 mmol), sodium carbonate (0.16 g, 1.50 mmol), and dichloromethane (10 mL) were added to a vial and the mixture stirred at room temperature for 12 hours. After the reaction was completed, the reactants were filtered with celite (dichloromethane (15 mL×3)), the solvent was removed by distillation under reduced pressure, and separation and purification were performed by column chromatography (n-hexane/acetone=2:1 to 1:1) to prepare Catalyst D.

8-[N—(N,N-Dimethylaminocarbonyl) amino]quinoline Bound Cp*-Iridium Complex (Catalyst D)

(11) ##STR00019##
Red solid (0.15 g, 51%); .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.47 (d, J=5.0 Hz, 1H), 7.92 (d, J=8.4 Hz, 1H), 7.34-7.28 (m, 2H), 6.93 (d, J=8.0 Hz, 1H), 6.68 (d, J=7.9 Hz, 1H), 3.17 (s, 6H), 1.62 (s, 15H); .sup.13C NMR (150 MHz, CDCl.sub.3, two carbons merged to others) δ 166.5, 154.8, 147.0, 145.0, 137.7, 130.5, 129.9, 121.7, 115.6, 111.6, 86.0 (Cp*), 8.4 (Cp*); IR (cm.sup.−1) 2910, 1622, 1460, 1358, 1327, 1150, 811, 772; HRMS (EI) m/z calcd. for C.sub.22H.sub.27ClIrN.sub.3O [M].sup.+: 577.1472. found: 577.1475.

Preparation Example I: Preparation of Hydroxamic Acid

(12) One-Pot Synthesis of Hydroxamic Acids from Carboxylic Acids

(13) ##STR00020##

(14) Carboxylic acid (10 mmol) was added to dried tetrahydrofuran (THF, 30 mL), and 1,1′-carbonyldiimidazole (CDI, 15 mmol, 1.5 equiv) was added thereto and the mixture was stirred for 1 hour. Hydroxylamine hydrochloride (1.39 g, 20 mmol) in a powder form was added and the mixture was stirred for 16 hours. After the reaction was completed, the reaction mixture was added to a 5% aqueous KHSO.sub.4 solution (30 mL), and extracted with EtOAc (2×30 mL). The collected organic layer was washed with a saline (50 mL), dried with MgSO.sub.4, concentrated, and separated and purified by column chromatography (eluent: n-hexane/EtOAc, 1:1 to 1:5) to obtain the desired hydroxamic acid compound.

[Preparation Example 1] Preparation of 2-(3-methoxyphenyl)acetylhydroxamic Acid

(15) ##STR00021##
Prepared from 2-(3-methoxyphenyl) acetic acid (10 mmol scale); White solid (1.42 g, 78%); m.p. 115-117° C.; .sup.1H NMR (600 MHz, DMSO-d.sub.6) δ 10.62 (s, 1H), 8.81 (s, 1H), 7.20 (t, J=7.8 Hz, 1H), 6.86-6.77 (m, 3H), 3.73 (s, 3H), 3.25 (s, 2H); .sup.13C NMR (150 MHz, DMSO-d.sub.6) δ 166.9, 159.1, 137.5, 129.2, 121.2, 114.7, 111.8, 55.0, 39.4; IR (cm.sup.−1) 3193, 3031, 2895, 1625, 1488, 1256, 1047, 761; HRMS (EI) m/z calcd. for C.sub.9H.sub.11NO.sub.3 [M].sup.+: 181.0739. found: 181.0736.

[Preparation Example 2] Preparation of 2-(3,4-dimethoxyphenyl)acetylhydroxamic Acid

(16) ##STR00022##
Prepared from 2-(3,4-dimethoxyphenyl)acetic acid (5 mmol scale); White solid (0.57 mg, 54%); m.p. 144-146° C.; .sup.1H NMR (600 MHz, DMSO-d.sub.6) δ 10.57 (s, 1H), 8.78 (s, 1H), 6.88-6.85 (m, 2H), 6.76 (d, J=8.1 Hz, 1H), 3.73 (s, 3H), 3.71 (s, 3H), 3.20 (s, 2H); .sup.13C NMR (150 MHz, DMSO-d.sub.6) δ 167.2, 148.5, 147.5, 128.4, 120.9, 112.9, 111.8, 55.6, 55.4, 38.9; IR (cm.sup.−1) 3169, 3010, 1631, 1515, 1259, 1160, 1019, 601; HRMS (EI) m/z calcd. for C.sub.10H.sub.13NO.sub.4 [M].sup.+: 211.0845. found: 211.0843.

[Preparation Example 3] Preparation of 2-(3-methylphenyl)acetylhydroxamic Acid

(17) ##STR00023##
Prepared from 2-(3-methylphenyl)acetic acid (10 mmol scale); White solid (1.17 g, 71%); m.p. 128-130° C.; .sup.1H NMR (600 MHz, DMSO-d.sub.6) δ 10.63 (s, 1H), 8.81 (s, 1H), 7.17 (t, J=7.5 Hz, 1H), 7.07 (s, 1H), 7.05-7.02 (m, 2H), 3.23 (s, 2H), 2.28 (s, 3H); .sup.13C NMR (150 MHz, DMSO-d.sub.6, one carbon merged to others) δ 167.0, 137.2, 135.9, 129.5, 128.1, 127.0, 126.0, 21.0; IR (cm.sup.−1) 3159, 3004, 2865, 1628, 1555, 1049, 682, 542; HRMS (EI) m/z calcd. for C.sub.9H.sub.11NO.sub.2 [M].sup.+: 165.0790. found: 165.0788.

[Preparation Example 4] Preparation of 2-(3-chlorophenyl)acetylhydroxamic Acid

(18) ##STR00024##
Prepared from 2-(3-chlorophenyl)acetic acid (10 mmol scale); White solid (0.92 g, 50%); m.p. 128-130° C.; .sup.1H NMR (600 MHz, DMSO-d.sub.6) δ 10.67 (s, 1H), 8.87 (s, 1H), 7.36-7.26 (m, 3H), 7.21 (d, J=7.4 Hz, 1H), 3.30 (s, 2H); .sup.13C NMR (150 MHz, DMSO-d.sub.6) δ 166.4, 138.5, 132.8, 130.0, 128.7, 127.7, 126.4, 38.9; IR (cm.sup.−1) 3174, 3009, 2897, 1633, 1538, 1052, 617; HRMS (EI) m/z calcd. for C.sub.8H.sub.8ClNO.sub.2 [M].sup.+: 185.0244. found: 185.0241.

[Preparation Example 5] Preparation of 3-phenylpropanyl Hydroxamic Acid

(19) ##STR00025##
Prepared from 3-phenylpropanoic acid (5.0 mmol scale); White solid (0.75 g, 91%); m.p. 87-89° C.; .sup.1H NMR (600 MHz, DMSO-d.sub.6) δ 10.38 (s, 1H), 8.72 (s, 1H), 7.27 (t, J=7.5 Hz, 2H), 7.23-7.13 (m, 3H), 2.80 (t, J=7.7 Hz, 2H), 2.25 (t, J=7.7 Hz, 2H); .sup.13C NMR (150 MHz, DMSO-d.sub.6) δ 168.2, 141.1, 128.3, 128.2, 125.9, 33.9, 30.8; IR (cm.sup.−1) 3285, 2766, 1604, 1059, 694; HRMS (FAB) m/z calcd. for C.sub.9H.sub.11NO.sub.2 [M+H].sup.+: 166.0868. found: 166.0869.

[Preparation Example 6] Preparation of 3-(2-bromophenyl)propanyl Hydroxamic Acid

(20) ##STR00026##
Prepared from 3-(2-bromophenyl)propanoic acid (5.0 mmol scale); White solid (1.15 g, 85%); m.p. 104-106° C.; .sup.1H NMR (600 MHz, DMSO-d.sub.6) δ 10.42 (s, 1H), 8.74 (s, 1H), 7.58 (d, J=7.9 Hz, 1H), 7.34-7.28 (m, 2H), 7.21-7.11 (m, 1H), 2.91 (t, J=7.7 Hz, 2H), 2.27 (t, J=7.7 Hz, 2H); .sup.13C NMR (150 MHz, DMSO-d.sub.6) δ 167.8, 140.0, 132.5, 130.5, 128.3, 127.9, 123.6, 32.1, 31.2; IR (cm.sup.−1) 3160, 3041, 1618, 1024, 743; HRMS (FAB) m/z calcd. for C.sub.9H.sub.10BrNO.sub.2 [M+H].sup.+: 243.9973. found: 243.9975.

[Preparation Example 7] Preparation of 3-(3,4-dimethoxyphenyl)propanoylhydroxamic Acid

(21) ##STR00027##
Prepared from 3-(3,4-dimethoxyphenyl)propanoic acid (10 mmol scale); White solid (1.14 g, 50%); m.p. 105-107° C.; .sup.1H NMR (600 MHz, DMSO-d.sub.6) δ 10.35 (s, 1H), 8.69 (s, 1H), 6.83 (d, J=8.1 Hz, 1H), 6.79 (s, 1H), 6.69 (d, J=8.1 Hz, 1H), 3.73 (s, 3H), 3.70 (s, 3H), 2.74 (t, J=7.7 Hz, 2H), 2.23 (t, J=7.7 Hz, 2H); .sup.13C NMR (150 MHz, DMSO-d.sub.6) δ 168.3, 148.6, 147.1, 133.5, 119.9, 112.2, 111.9, 55.5, 55.4, 34.2, 30.5; IR (cm.sup.−1) 3191, 3003, 2909, 1631, 1512, 1144, 553; HRMS (EI) m/z calcd. for C.sub.11H.sub.15NO.sub.4 [M].sup.+: 225.1001. found: 225.1003.

Preparation Example II: Preparation of 3-substituted-1,4,2-dioxazol-5-one Compound

(22) A hydroxamic acid compound (5.0 mmol) was dissolved in dichloromethane (50 mL), 1,1′ (0.81 g, 5.0 mmol) was added thereto all together at room temperature, and the mixture was stirred for 30 minutes. After the reaction was completed, the product was quenched with 1 N HCl (30 mL), extracted with dichloromethane (50 mL×3), and dried with magnesium sulfate, and the solvent was removed solvent. The residue was filtered with silica and washed with dichloromethane (10 ml×2), and then the filtrate was distilled under reduced pressure to obtain the title compound.

(23) The following compound was prepared in the same manner as in the above, except that the starting material was changed.

[Preparation Example 8] Preparation of 3-(3-ethoxybenzyl)-1,4,2-dioxazol-5-one

(24) ##STR00028##
Prepared on a 2 mmol scale; White solid (331 mg, 92%); m.p. 44-46° C.; .sup.1H NMR (400 MHz, CDCl.sub.3) δ 7.33-7.27 (m, 1H), 6.91-6.86 (m, 2H), 6.83-6.81 (m, 1H), 3.89 (s, 2H), 3.82 (s, 3H); .sup.13C NMR (100 MHz, CDCl.sub.3) δ 165.4, 160.3, 154.0, 131.9, 130.4, 121.3, 114.9, 113.9, 55.5, 31.4; IR (cm.sup.−1) 3079, 3011, 2842, 1810, 1348, 1147, 986, 745; HRMS (EI) m/z calcd. for C.sub.10H.sub.9NO.sub.4 [M].sup.+: 207.0532. found: 207.0532.

[Preparation Example 9] Preparation of 3-(3,4-dimethoxybenzyl)-1,4,2-dioxazol-5-one

(25) ##STR00029##
Prepared on a 2 mmol scale; White solid (421 mg, 89%); m.p. 73-75° C.; .sup.1H NMR (400 MHz, CDCl.sub.3) δ 6.88-6.82 (m, 2H), 6.79-6.76 (m, 1H), 3.89 (s, 3H), 3.88 (s, 3H), 3.87 (s, 2H); .sup.13C NMR (150 MHz, CDCl.sub.3) δ 165.6, 154.1, 149.7, 149.4, 122.7, 121.6, 112.1, 111.9, 56.2, 56.1, 31.0; IR (cm.sup.−1) 3001, 2929, 2845, 1821, 1511, 1142, 987; HRMS (EI) m/z calcd. for C.sub.11H.sub.11NO.sub.5 [M].sup.+: 237.0637. found: 237.0639.

[Preparation Example 10] Preparation of 3-(3-methylbenzyl)-1,4,2-dioxazol-5-one

(26) ##STR00030##
Prepared on a 2 mmol scale; Colorless liquid (353 mg, 93%); .sup.1H NMR (400 MHz, CDCl.sub.3) δ 7.3 (t, J=7.6 Hz, 1H), 7.16 (d, J=7.6 Hz, 1H), 7.12-7.04 (m, 2H), 3.87 (s, 2H), 2.36 (s, 3H); .sup.13C NMR (100 MHz, CDCl.sub.3) δ 165.5, 154.1, 139.2, 130.4, 129.8, 129.3, 129.2, 126.1, 31.2, 21.4; IR (cm.sup.−1) 3022, 2922, 1824, 1349, 1143, 981, 744; HRMS (EI) m/z calcd. for C.sub.10H.sub.9NO.sub.3 [M].sup.+: 191.0582. found: 191.0581.

[Preparation Example 11] Preparation of 3-(3-chlorobenzyl)-1,4,2-dioxazol-5-one

(27) ##STR00031##
Prepared on a 1 mmol scale; White solid (187 mg, 88%); m.p. 49-51° C.; .sup.1H NMR (600 MHz, CDCl.sub.3) δ 7.37-7.29 (m, 3H), 7.19 (d, J=6.8 Hz, 1H), 3.92 (s, 2H); .sup.13C NMR (150 MHz, CDCl.sub.3) δ 164.8, 153.8, 135.2, 132.3, 130.6, 129.3, 128.9, 127.3, 30.9; IR (cm.sup.−1) 3064, 2921, 1865, 1831, 1245, 993, 721; HRMS (EI) m/z calcd. for C.sub.9H.sub.6ClNO.sub.3 [M].sup.+: 211.0036. found: 211.0035.

[Preparation Example 12] Preparation of 3-phenethyl-1,4,2-dioxazol-5-one

(28) ##STR00032##
Prepared on a 2.0 mmol scale; White solid (0.36 g, 95%); m.p. 38-40° C.; .sup.1H NMR (600 MHz, CDCl.sub.3) δ 7.33 (t, J=7.4 Hz, 2H), 7.29-7.23 (m, 1H), 7.19 (d, J=7.4 Hz, 2H), 3.03 (t, J=7.7 Hz, 2H), 2.94 (t, J=7.7 Hz, 2H); .sup.13C NMR (150 MHz, CDCl.sub.3) δ 166.0, 154.1, 138.1, 129.0, 128.3, 127.3, 30.6, 26.8; IR (cm.sup.−1) 1815, 1636, 1149, 980, 694; HRMS (FAB) m/z calcd. for C.sub.10H.sub.9NO.sub.3 [M+H].sup.+: 192.0661. found: 192.0663.

[Preparation Example 13] Preparation of 3-(2-bromophenethyl)-1,4,2-dioxazol-5-one

(29) ##STR00033##
Prepared on a 5.0 mmol scale. White solid (1.04 g, 85%); m.p. 71-73° C.; .sup.1H NMR (600 MHz, CDCl.sub.3) δ 7.6 (d, J=8.0 Hz, 1H), 7.28 (t, J=7.4 Hz, 1H), 7.25 (t, J=6.9 Hz, 1H), 7.15 (t, J=7.4 Hz, 1H), 3.16 (t, J=7.7 Hz, 2H), 2.98 (t, J=7.7 Hz, 2H); .sup.13C NMR (150 MHz, CDCl.sub.3) δ 165.7, 154.1, 137.5, 133.4, 130.6, 129.2, 128.1, 124.3, 31.3, 25.2; IR (cm.sup.−1) 1862, 1831, 1632, 1150, 755; HRMS (FAB) m/z calcd. for C.sub.10H.sub.8BrNO.sub.3 [M+H].sup.+: 269.9766. found: 269.9763.

[Preparation Example 14] Preparation of 3-(3,4-dimethoxyphenethyl)-1,4,2-dioxazol-5-one

(30) ##STR00034##
Prepared on a 2 mmol scale; White solid (409 mg, 82%); m.p. 59-61° C.; .sup.1H NMR (600 MHz, CDCl.sub.3) δ 6.82 (d, J=8.1 Hz, 1H), 6.74 (d, J=8.1 Hz, 1H), 6.70 (s, 1H), 3.87 (s, 3H), 3.86 (s, 3H), 2.98 (t, J=7.1 Hz, 2H), 2.92 (t, J=7.1 Hz, 2H); .sup.13C NMR (150 MHz, CDCl.sub.3) δ 166.0, 154.1, 149.3, 148.3, 130.6, 120.3, 111.7, 111.6, 56.1, 56.0, 30.3, 27.1; IR (cm.sup.−1) 2962, 2936, 2838, 1821, 1512, 1134, 754; HRMS (EI) m/z calcd. for C.sub.12H.sub.13NO.sub.5 [M].sup.+: 251.0794. found: 251.0795.

[Preparation Example 15] Preparation of 3-(4-methoxyphenethyl)-1,4,2-dioxazol-5-one

(31) ##STR00035##
Prepared on a 2 mmol scale; White solid (420 mg, 95%); m.p. 39-41° C.; .sup.1H NMR (600 MHz, CDCl.sub.3) δ 7.12 (d, J=8.6 Hz, 2H), 6.86 (d, J=8.6 Hz, 2H), 3.80 (s, 3H), 2.98 (t, J=7.4 Hz, 2H), 2.90 (t, J=7.4 Hz, 2H); .sup.13C NMR (150 MHz, CDCl.sub.3) δ 166.0, 158.8, 154.2, 130.1, 129.4, 114.5, 55.4, 29.8, 27.1; IR (cm.sup.−1) 3000, 2914, 2834, 1828, 1512, 1222, 750; HRMS (EI) m/z calcd. for C.sub.11H.sub.11NO.sub.4 [M].sup.+: 221.0688. found: 221.0690.

[Preparation Example 16] Preparation of 3-(4-hydroxyphenethyl)-1,4,2-dioxazol-5-one

(32) ##STR00036##
Prepared on 2 mmol scale; White solid (0.20 g, 50%); m.p. 77-79° C.; .sup.1H NMR (600 MHz, CDCl.sub.3) δ 7.07 (d, J=8.4 Hz, 2H), 6.79 (d, J=8.4 Hz, 2H), 4.84 (br, 1H), 2.97 (t, J=7.5 Hz, 2H), 2.90 (t, J=7.5 Hz, 2H); .sup.13C NMR (150 MHz, CDCl.sub.3) δ 166.0, 154.8, 154.2, 130.3, 129.6, 115.9, 29.9, 27.1; IR (cm.sup.−1) 3454, 2918, 1810, 1513, 1166, 985, 825; HRMS (EI) m/z calcd. for C.sub.10H.sub.9NO.sub.4 [M].sup.+: 207.0532. found: 207.0529.

[Preparation Example 17] Preparation of 3-(4-hydroxy-3-methoxyphenethyl)-1,4,2-dioxazol-5-one

(33) ##STR00037##
Prepared on a 2 mmol scale; White solid (0.19 g, 41%); m.p. 96-98° C.; .sup.1H NMR (600 MHz, CDCl.sub.3) δ 6.87 (d, J=8.0 Hz, 1H), 6.73-6.64 (m, 2H), 5.55 (s, 1H), 3.88 (s, 3H), 2.99-2.95 (m, 2H), 2.94-2.88 (m, 2H); .sup.13C NMR (150 MHz, CDCl.sub.3) δ 166.0, 154.2, 146.8, 144.9, 130.0, 121.0, 114.9, 110.9, 56.1, 30.4, 27.2; IR (cm.sup.−1) 3471, 1827, 1510, 1257, 981, 817; HRMS (EI) m/z calcd. for C.sub.11H.sub.11NO.sub.5 [M].sup.+: 237.0637. found: 237.0635.

[Preparation Example 18] Preparation of 3-(3-bromo-4-hydroxyphenethyl)-1,4,2-dioxazol-5-one

(34) ##STR00038##
Prepared on a 1 mmol scale; White solid (0.07 g, 24%); m.p. 71-73° C.; .sup.1H NMR (400 MHz, CDCl.sub.3) δ 7.32 (s, 1H), 7.05 (d, J=8.3 Hz, 1H), 6.97 (d, J=8.3 Hz, 1H), 5.51 (s, 1H), 3.45-2.01 (m, 4H); .sup.13C NMR (150 MHz, CDCl.sub.3) δ 165.7, 154.0, 151.6, 131.8, 131.7, 129.2, 116.6, 110.6, 29.4, 26.9; IR (cm.sup.−1) 3344, 1816, 1649, 1419, 1169, 985, 769; HRMS (EI) m/z calcd. for C.sub.10H.sub.8BrNO.sub.4 [M].sup.+: 284.9637. found: 284.9639.

[Preparation Example 19] Preparation of 3-(4-hydroxy-2-methoxyphenethyl)-1,4,2-dioxazol-5-one

(35) ##STR00039##
Prepared on 1 mmol scale; Colorless oil (0.05 g, 22%); .sup.1H NMR (600 MHz, CDCl.sub.3) δ 6.93 (d, J=8.1 Hz, 1H), 6.40 (s, 1H), 6.34 (d, J=8.1 Hz, 1H), 3.77 (s, 3H), 2.92 (t, J=7.2 Hz, 2H), 2.85 (t, J=7.2 Hz, 2H); .sup.13C NMR (150 MHz, CDCl.sub.3) δ 166.6, 158.6, 156.4, 154.6, 130.7, 118.5, 107.1, 99.2, 55.4, 25.8, 25.5; IR (cm.sup.−1) 3333, 2938, 1817, 1596, 1288, 1151, 831; HRMS (EI) m/z calcd. for C.sub.11H.sub.11NO.sub.5 [M].sup.+: 237.0637. found: 237.0639.

[Preparation Example 20] Preparation of 3-(4-hydroxy-3,5-methoxyphenethyl)-1,4,2-dioxazol-5-one

(36) ##STR00040##
Prepared on a 1 mmol scale; White solid (0.08 g, 36%); m.p. 100-102° C.; .sup.1H NMR (600 MHz, CDCl.sub.3) δ 6.81 (s, 2H), 4.65 (s, 1H), 2.93-2.85 (m, 4H), 2.23 (s, 6H); .sup.13C NMR (150 MHz, CDCl.sub.3) δ 166.2, 154.3, 151.4, 129.7, 128.4, 123.6, 29.9, 27.1, 16.0; IR (cm.sup.−1) 3459, 2942, 1861, 1418, 1202, 1149, 984; HRMS (EI) m/z calcd. for C.sub.12H.sub.13NO.sub.4 [M].sup.+: 235.0845. found: 235.0843.

[Preparation Example 21] Preparation of 2-{2-(4-hydroxyphenyl)-1-(5-oxo-1,4,2-dioxazol-3-yl)ethyl}isoindoline-1,3-dione

(37) ##STR00041##
Prepared on 1 mmol scale; White solid (0.11 g, 31%); m.p. 153-155° C.; .sup.1H NMR (600 MHz, CDCl.sub.3) δ 7.85-7.79 (m, 2H), 7.79-7.70 (m, 2H), 7.05 (d, J=8.2 Hz, 2H), 6.68 (d, J=8.2 Hz, 2H), 5.54 (dd, J=10.2, 5.6 Hz, 1H), 3.63-3.40 (m, 2H); .sup.13C NMR (150 MHz, CDCl.sub.3) δ 166.8, 163.8, 155.2, 153.4, 134.9, 131.2, 130.5, 126.4, 124.1, 115.9, 46.7, 33.1; IR (cm.sup.−1) 3371, 1855, 1705, 1387, 1310, 991, 711; HRMS (EI) m/z calcd. for C.sub.18H.sub.12N.sub.2O.sub.6 [M].sup.+: 352.0695. found: 352.0699.

[Preparation Example 22] Preparation of 3-(2-hydroxy-4-methoxyphenethyl)-1,4,2-dioxazol-5-one

(38) ##STR00042##
Prepared on a 1 mmol scale; White solid (0.05 g, 22%); m.p. 59-61° C.; .sup.1H NMR (600 MHz, CDCl.sub.3) δ 7.00 (d, J=8.3 Hz, 1H), 6.44 (d, J=8.3 Hz, 1H), 6.34 (s, 1H), 5.57 (br, 1H), 3.76 (s, 3H), 2.97 (t, J=6.7 Hz, 2H), 2.92 (t, J=6.7 Hz, 2H); .sup.13C NMR (150 MHz, CDCl.sub.3) δ 166.6, 160.0, 154.7, 154.5, 131.2, 117.2, 106.1, 102.4, 55.5, 25.5, 25.4; IR (cm.sup.−1) 3417, 2951, 1823, 1521, 1212, 1113, 978; HRMS (EI) m/z calcd. for C.sub.11H.sub.11NO.sub.5 [M].sup.+: 237.0637. found: 237.0640.

[Preparation Example 23] Preparation of 3-{2-(2-hydroxynaphthalen-1-yl)ethyl}-1,4,2-dioxazol-5-one

(39) ##STR00043##
Prepared on a 1 mmol scale; Yellow resin (0.07 g, 27%); .sup.1H NMR (600 MHz, CDCl.sub.3) δ 7.84 (d, J=8.6 Hz, 1H), 7.81 (d, J=8.1 Hz, 1H), 7.69 (d, J=8.8 Hz, 1H), 7.54 (t, J=7.7 Hz, 1H), 7.37 (t, J=7.5 Hz, 1H), 7.03 (d, J=8.8 Hz, 1H), 5.47 (br, 1H), 3.49 (t, J=7.4 Hz, 2H), 2.99 (t, J=7.4 Hz, 2H); .sup.13C NMR (150 MHz, CDCl.sub.3) δ 166.6, 154.5, 151.1, 132.8, 129.6, 129.3, 129.2, 127.4, 123.6, 121.8, 117.8, 116.4, 24.8, 20.4; IR (cm.sup.−1) 3394, 3065, 1823, 1627, 1513, 1276, 988, 745; HRMS (EI) m/z calcd. for C.sub.14H.sub.11NO.sub.4 [M].sup.+: 257.0688. found: 257.0689.

[Preparation Example 24] Preparation of 3-(4-hydroxybenzyl)-1,4,2-dioxazol-5-one

(40) ##STR00044##
Prepared on a 2 mmol scale; Colorless oil (0.22 g, 56%); .sup.1H NMR (600 MHz, CDCl.sub.3) δ 7.15 (d, J=8.3 Hz, 2H), 6.83 (d, J=8.3 Hz, 2H), 5.34 (br, 1H), 3.85 (s, 2H); .sup.13C NMR (150 MHz, CDCl.sub.3) δ 165.7, 155.9, 154.2, 130.5, 122.5, 116.3, 30.6; IR (cm.sup.−1) 3413, 1818, 1513, 1215, 1145, 983, 756; HRMS (EI) m/z calcd. for C.sub.9H.sub.7NO.sub.4 [M].sup.+: 193.0375. found: 193.0371.

[Preparation Example 25] Preparation of 3-{2-(4-methoxy-1H-indol-3-yl)ethyl}-1,4,2-dioxazol-5-one

(41) ##STR00045##
Prepared on a 1 mmol scale; Pale yellow solid (0.05 g, 26%); m.p. 131-133° C.; .sup.1H NMR (600 MHz, CDCl.sub.3) δ 7.98 (br, 1H), 7.12 (t, J=8.0 Hz, 1H), 6.98 (d, J=7.9 Hz, 1H), 6.90 (s, 1H), 6.52 (d, J=7.6 Hz, 1H), 3.94 (s, 3H), 3.26 (t, J=6.9 Hz, 2H), 3.05 (t, J=6.9 Hz, 2H); .sup.13C NMR (150 MHz, CDCl.sub.3) δ 166.9, 154.6, 154.5, 138.3, 123.5, 121.0, 116.9, 113.4, 104.8, 99.8, 55.3, 27.4, 22.8; IR (cm.sup.−1) 3414, 2926, 1812, 1507, 1079, 981, 734; HRMS (EI) m/z calcd. for C.sub.13H.sub.12N.sub.2O.sub.4 [M].sup.+: 260.0797. found: 260.0794.

[Preparation Example 26] Preparation of 3-{2-(1-methyl-1H-indol-3-yl)ethyl}-1,4,2-dioxazol-5-one

(42) ##STR00046##
Prepared on a 1 mmol scale; Brown solid (0.12 g, 48%); m.p. 78-80° C.; .sup.1H NMR (600 MHz, CDCl.sub.3) δ 7.55 (d, J=8.0 Hz, 1H), 7.32 (d, J=8.2 Hz, 1H), 7.29-7.24 (m, 1H), 7.15 (t, J=7.5 Hz, 1H), 6.91 (s, 1H), 3.76 (s, 3H), 3.20 (t, J=7.5 Hz, 2H), 3.01 (t, J=7.5 Hz, 2H); .sup.13C NMR (150 MHz, CDCl.sub.3) δ 166.4, 154.3, 137.2, 127.2, 126.8, 122.2, 119.4, 118.4, 111.1, 109.7, 32.8, 26.2, 20.6; IR (cm.sup.−1) 2926, 1825, 1412, 1328, 1154, 976, 753; HRMS (EI) m/z calcd. for C.sub.13H.sub.12N.sub.2O.sub.3 [M].sup.+: 244.0848. found: 244.0849.

[Preparation Example 27] Preparation of 3-(4-methylphenethyl)-1,4,2-dioxazol-5-one

(43) ##STR00047##
Prepared on a 2 mmol scale; White solid (0.40 g, 97%); m.p. 35-37° C.; .sup.1H NMR (600 MHz, CDCl.sub.3) δ 7.14 (d, J=7.8 Hz, 2H), 7.09 (d, J=7.8 Hz, 2H), 3.00 (t, J=7.6 Hz, 2H), 2.92 (t, J=7.6 Hz, 2H), 2.34 (s, 3H); .sup.13C NMR (150 MHz, CDCl.sub.3) δ 166.0, 154.2, 136.9, 135.1, 129.7, 128.2, 30.2, 26.9, 21.2; IR (cm.sup.−1) 2924, 1861, 1815, 1629, 1337, 1147, 984, 788; HRMS (EI) m/z calcd. for C.sub.11H.sub.11NO.sub.3 [M].sup.+: 205.0739. found: 205.0738.

[Preparation Example 28] Preparation of 3-(4-chlorophenethyl)-1,4,2-dioxazol-5-one

(44) ##STR00048##
Prepared on a 2 mmol scale; Yellow oil (0.50 g, 98%); .sup.1H NMR (600 MHz, CDCl.sub.3) δ 7.31 (d, J=8.3 Hz, 2H), 7.14 (d, J=8.3 Hz, 2H), 3.02 (t, J=7.6 Hz, 2H), 2.93 (t, J=7.6 Hz, 2H); .sup.13C NMR (150 MHz, CDCl.sub.3) δ 165.7, 154.0, 136.5, 133.3, 129.7, 129.3, 29.9, 26.7; IR (cm.sup.−1) 1866, 1823, 1635, 1491, 1091, 978, 758; HRMS (EI) m/z calcd. for C.sub.10H.sub.8ClNO.sub.3 [M].sup.+: 225.0193. found: 225.0192.

[Preparation Example 29] Preparation of 3-{4-(trifluoromethyl)phenethyl}-1,4,2-dioxazol-5-one

(45) ##STR00049##
Prepared on a 2 mmol scale; Yellow oil (0.32 g, 61%); 1H NMR (600 MHz, CDCl.sub.3) δ 7.60 (d, J=7.9 Hz, 2H), 7.34 (d, J=7.9 Hz, 2H), 3.11 (t, J=7.7 Hz, 2H), 2.98 (t, J=7.7 Hz, 2H); .sup.13C NMR (150 MHz, CDCl.sub.3) δ 165.6, 154.0, 142.1, 129.8 (q, J=33.0 Hz), 128.8, 126.1, 124.2 (q, J=271.9 Hz), 30.2, 26.4; .sup.19F NMR (564 MHz, CDCl.sub.3) δ −62.6; IR (cm.sup.−1) 1868, 1825, 1321, 1107, 979, 825, 760; HRMS (EI) m/z calcd. for C.sub.11H.sub.8F.sub.3NO.sub.3 [M].sup.+: 259.0456. found: 259.0454.

[Preparation Example 30] Preparation of 3-{2-(4-methoxyphenyl)-2-phenylethyl}-1,4,2-dioxazol-5-one

(46) ##STR00050##
Prepared on a 1 mmol scale; Yellow oil (0.28 g, 97%); .sup.1H NMR (600 MHz, CDCl.sub.3) δ 7.33 (appt, J=7.4 Hz, 2H), 7.28-7.20 (m, 3H), 7.16 (d, J=8.4 Hz, 2H), 6.86 (d, J=8.4 Hz, 2H), 4.43 (t, J=8.2 Hz, 1H), 3.78 (s, 3H), 3.33 (d, J=8.2 Hz, 2H); .sup.13C NMR (150 MHz, CDCl.sub.3) δ 165.2, 158.9, 154.0, 141.8, 133.4, 129.4, 129.1, 128.6, 127.5, 114.5, 55.4, 46.1, 31.5; IR (cm.sup.−1) 2935, 2836, 1823, 1510, 1246, 979, 698; HRMS (EI) m/z calcd. for C.sub.17H.sub.15NO.sub.4 [M].sup.+: 297.1001. found: 297.1004.

[Preparation Example 31] Preparation of 3-(2-methylphenethyl)-1,4,2-dioxazol-5-one

(47) ##STR00051##
Prepared on a 2 mmol scale; White solid (0.38 g, 92%); m.p. 86-88° C.; .sup.1H NMR (600 MHz, CDCl.sub.3) δ 7.22-7.06 (m, 4H), 3.04 (t, J=7.8 Hz, 2H), 2.90 (t, J=7.8 Hz, 2H), 2.34 (s, 3H); .sup.13C NMR (150 MHz, CDCl.sub.3) δ 166.1, 154.2, 136.4, 136.0, 130.9, 128.6, 127.5, 126.7, 28.1, 25.6, 19.3; IR (cm.sup.−1) 3011, 1831, 1605, 1388, 1151, 984, 742; HRMS (EI) m/z calcd. for C.sub.11H.sub.11NO.sub.3 [M].sup.+: 205.0739. found: 205.0739.

[Preparation Example 32] Preparation of 3-(2,2,2-triphenylethyl)-1,4,2-dioxazol-5-one

(48) ##STR00052##
Prepared on a 2 mmol scale; White solid (0.29 g, 43%); m.p. 170-172° C.; 1H NMR (600 MHz, CDCl.sub.3) δ 7.40-7.23 (m, 15H), 4.00 (s, 2H); .sup.13C NMR (150 MHz, CDCl.sub.3) δ 165.0, 153.7, 144.8, 128.8, 128.4, 127.1, 56.3, 37.0; IR (cm.sup.−1) 3056, 1818, 1366, 1149, 977, 697; HRMS (EI) m/z calcd. for C22H.sub.17NO.sub.3 [M].sup.+: 343.1208. found: 343.1212.

[Preparation Example 33] Preparation of 3-{2-(Naphthalen-1-yl)ethyl}-1,4,2-dioxazol-5-one

(49) ##STR00053##
Prepared on a 2 mmol scale; White solid (0.20 g, 42%); m.p. 78-80° C.; 1H NMR (600 MHz, CDCl.sub.3) δ 7.98-7.93 (m, 1H), 7.93-7.88 (m, 1H), 7.83-7.75 (m, 1H), 7.58 (t, J=7.2 Hz, 1H), 7.53 (t, J=7.2 Hz, 1H), 7.43 (t, J=7.6 Hz, 1H), 7.39-7.32 (m, 1H), 3.50 (t, J=7.9 Hz, 2H), 3.07 (t, J=7.9 Hz, 2H); .sup.13C NMR (150 MHz, CDCl.sub.3, one carbon merged to others) δ 166.1, 154.1, 134.2, 131.3, 129.4, 128.3, 126.8, 126.5, 126.1, 125.7, 122.8, 28.0, 26.1; IR (cm.sup.−1) 3045, 1828, 1633, 1317, 1154, 986, 761; HRMS (EI) m/z calcd. for C.sub.4H.sub.11NO.sub.3 [M].sup.+: 241.0739. found: 241.0739.

[Preparation Example 34] Preparation of 3-(4-Methoxybenzyl)-1,4,2-dioxazol-5-one

(50) ##STR00054##
Prepared on a 1 mmol scale; White solid (0.20 g, 96%); 1H NMR (600 MHz, CDCl.sub.3) δ 7.21 (d, J=8.6 Hz, 2H), 6.91 (d, J=8.6 Hz, 2H), 3.87 (s, 2H), 3.81 (s, 3H); .sup.13C NMR (150 MHz, CDCl.sub.3) δ 165.7, 159.8, 154.1, 130.3, 122.3, 114.8, 55.5, 30.6.

[Preparation Example 35] Preparation of 3-(3-methoxyphenethyl)-1,4,2-dioxazol-5-one

(51) ##STR00055##
Prepared on a 2 mmol scale; White solid (0.43 g, 97%); m.p. 35-37° C.; .sup.1H NMR (600 MHz, CDCl.sub.3) δ 7.25 (t, J=7.3 Hz, 1H), 6.84-6.76 (m, 2H), 6.74 (s, 1H), 3.80 (s, 3H), 3.00 (t, J=7.7 Hz, 2H), 2.93 (t, J=7.7 Hz, 2H); .sup.13C NMR (150 MHz, CDCl.sub.3) δ 166.0, 160.1, 154.1, 139.7, 130.1, 120.6, 114.3, 112.5, 55.4, 30.6, 26.7; IR (cm.sup.−1) 2940, 1826, 1583, 1257, 1151, 982, 782, 693; HRMS (EI) m/z calcd. for C.sub.11H.sub.11NO.sub.4 [M].sup.+: 221.0688. found: 221.0686.

[Preparation Example 36] Preparation of 3-(3-Bromophenethyl)-1,4,2-dioxazol-5-one

(52) ##STR00056##
Prepared on a 2 mmol scale; Colorless oil (0.51 g, 95%); .sup.1H NMR (600 MHz, CDCl.sub.3) δ 7.41 (d, J=8.0 Hz, 1H), 7.37 (s, 1H), 7.21 (t, J=7.8 Hz, 1H), 7.14 (d, J=7.6 Hz, 1H), 3.02 (t, J=7.6 Hz, 2H), 2.98-2.90 (t, J=7.6 Hz, 2H); .sup.13C NMR (150 MHz, CDCl.sub.3) δ 165.6, 154.0, 140.4, 131.5, 130.6, 130.5, 127.0, 123.1, 30.1, 26.6; IR (cm.sup.−1) 1866, 1823, 1634, 1145, 978, 757, 684; HRMS (EI) m/z calcd. for C.sub.10H.sub.8BrNO.sub.3 [M].sup.+: 268.9688. found: 268.9690.

EXAMPLE II: PREPARATION LACTAM COMPOUND FROM 3-SUBSTITUTED DIOXAZOL-ONE COMPOUND

(53) ##STR00057##

(54) An iridium catalyst (Catalyst A, 2.6 mg, 5.0 mol %), sodium tetrakis[3,5-bis(trifluoromethyl)phenyl]borate (NaBAr.sup.F.sub.4, 4.43 mg, 5.0 mol %), and hexafluoro-2-propanol (HFP) or dichloromethane (1.2 mL) were added to a well-dried vial under an argon atmosphere, the mixture was stirred for 1 minute, a 3-substituted dioxazol-one compound (0.1 mmol) was added thereto, and the vial was sealed under the argon atmosphere. Thereafter, the reaction mixture was vigorously stirred at 60° C. for 12 hours, cooled to room temperature, filtered with celite, washed with dichloromethane (10 mL×4), and then concentrated under reduced pressure. The concentrated residue was separated and purified with column chromatography (eluent: n-hexane/10% methanol-EtOAc solution, 2:1 to 1:1 or n-hexane/EtOAc, 2:1˜1:2) to obtain the desired lactam compound.

[Example 3] Preparation of 5-Methoxyindolin-2-one (1-A)/7-Methoxyindolin-2-one (1-B)

(55) ##STR00058##
DCM (1.2 mL) was used as a solvent, and the reaction was performed at room temperature. White solid (15 mg, 90%); a mixture of two isomers at a ratio of 3.0:1 was obtained.

(56) Major isomer (5-Methoxyindolin-2-one (1-A)) White solid; 1H NMR (600 MHz, CDCl.sub.3) δ 7.90 (s, 1H), 6.85 (s, 1H), 6.80-6.72 (m, 2H), 3.78 (s, 3H), 3.52 (s, 2H); .sup.13C NMR (150 MHz, CDCl.sub.3) δ 177.1, 155.9, 135.9, 126.8, 112.7, 112.0, 110.0, 56.0, 36.7.

(57) Minor isomer (7-Methoxyindolin-2-one (1-B)): White solid; .sup.1H NMR (600 MHz, CDCl.sub.3) δ 7.64 (s, 1H), 6.98 (t, J=7.9 Hz, 1H), 6.85 (d, J=7.4 Hz, 1H), 6.81 (d, J=8.2 Hz, 1H), 3.87 (s, 3H), 3.55 (s, 2H); .sup.13C NMR (150 MHz, CDCl.sub.3) δ 176.4, 143.8, 131.3, 126.1, 122.9, 117.1, 110.3, 55.8, 36.8.

[Example 4] Preparation of 5,6-dimethoxyindolin-2-one (2)

(58) ##STR00059##
HFP (1.2 mL) was used as a solvent. White solid (18 mg, 93%); .sup.1H NMR (600 MHz, CDCl.sub.3) δ 8.60 (s, 1H), 6.84 (s, 1H), 6.54 (s, 1H), 3.86 (s, 3H), 3.84 (s, 3H), 3.50 (s, 2H); .sup.13C NMR (100 MHz, CDCl.sub.3) δ 178.5, 149.5, 145.1, 136.2, 116.0, 109.8, 95.8, 57.0, 56.4, 36.6.

[Example 5] Preparation of 5-methylindolin-2-one (3-A)/7-methylindolin-2-one (3-B)

(59) ##STR00060##
HFP (1.2 mL) was used as a solvent. White solid (8 mg, 55%); a mixture of two isomers at a ratio of 3.0:1 was obtained, and regioselectivity was determined from .sup.1H NMR of the mixture in which regioisomers are mixed.

(60) Major isomer (5-Methylindolin-2-one (3-A)): .sup.1H NMR (600 MHz, CDCl.sub.3) δ 8.09 (s, 1H), 7.12-6.98 (m, 2H), 6.76 (d, J=7.8 Hz, 1H), 3.50 (s, 2H), 2.32 (s, 3H); .sup.13C NMR (150 MHz, CDCl.sub.3) δ 177.9, 140.1, 132.0, 128.3, 125.6, 125.5, 109.5, 36.4, 21.2.

(61) Minor isomer (7-methylindolin-2-one (3-B)): .sup.1H NMR (600 MHz, CDCl.sub.3) δ 8.55 (s, 1H), 7.12-6.98 (m, 2H), 6.94 (t, J=7.5 Hz, 1H), 3.56 (s, 2H), 2.28 (s, 3H); .sup.13C NMR (150 MHz, CDCl.sub.3) δ 178.4, 141.6, 129.3, 125.0, 122.4, 122.1, 119.4, 36.8, 16.6.

[Example 6] Preparation of 5-chloroindolin-2-one (4-A)/7-chloroindolin-2-one (4-B)

(62) ##STR00061##
HFP (1.2 mL) was used as a solvent. White solid (7 mg, 40%); a mixture of two isomers at a ratio of 1.5:1 was obtained.

(63) Major isomer (5-Chloroindolin-2-one (4-A)) White solid; .sup.1H NMR (600 MHz, CDCl.sub.3) δ 8.31 (s, 1H), 7.23-7.19 (m, 2H), 6.80 (d, J=8.1 Hz, 1H), 3.54 (s, 2H); .sup.13C NMR (150 MHz, CDCl.sub.3) δ 176.9, 141.0, 128.1, 127.9, 127.0, 125.3, 110.6, 36.3.

(64) Minor isomer (7-Chloroindolin-2-one (4-B)): White solid; .sup.1H NMR (400 MHz, CDCl.sub.3) δ 7.87 (s, 1H), 7.21 (d, J=8.6 Hz, 1H), 7.12 (d, J=6.8 Hz, 1H), 6.97 (t, J=7.8 Hz, 1H), 3.62 (s, 2H); .sup.13C NMR (150 MHz, CDCl.sub.3) δ 175.5, 140.0, 127.8, 126.4, 123.2, 122.9, 114.7, 36.9.

[Example 7] Preparation of 6,7-dimethoxy-3,4-dihydroquinolin-2(1H)-one (5)

(65) ##STR00062##

(66) HFP (1.2 mL) was used as a solvent. White solid (20 mg, 96%); .sup.1H NMR (600 MHz, CDCl.sub.3) δ 9.01 (s, 1H), 6.67 (s, 1H), 6.41 (s, 1H), 3.85 (s, 3H), 3.84 (s, 3H), 2.88 (t, J=7.6 Hz, 2H), 2.61 (t, J=7.6 Hz, 2H); .sup.13C NMR (150 MHz, CDCl.sub.3) δ 172.1, 148.6, 144.9, 130.8, 115.0, 111.8, 100.6, 56.5, 56.3, 31.1, 25.2.

EXAMPLE III: PREPARATION OF LACTAM COMPOUND FROM 3-SUBSTITUTED DIOXAZOL-ONE COMPOUND

(67) An iridium catalyst (Catalyst B, 2.9 mg, 5.0 mol %), sodium tetrakis[3,5-bis(trifluoromethyl)phenyl]borate (4.43 mg, 5.0 mol %), and hexafluoro-2-propanol (1.2 mL) were added to a well-dried vial under an argon atmosphere, the mixture was stirred for 1 minute, a 3-substituted dioxazol-one compound (0.1 mmol) was added, and the vial was sealed under the argon atmosphere. Thereafter, the reaction mixture was vigorously stirred at 60° C. for 12 hours, cooled to room temperature, filtered with celite, washed with dichloromethane (10 mL×4), and then concentrated under reduced pressure. The concentrated residue was separated and purified with column chromatography (eluent: n-hexane/10% methanol-EtOAc solution, 2:1 to 1:1 or n-hexane/EtOAc, 2:1˜1:2) to obtain the desired lactam compound.

[Example 8] Preparation of 6-methoxy-3,4-dihydroquinolin-2(1H)-one (6)

(68) ##STR00063##
White solid (18 mg, 99%); m.p. 140-142° C.; .sup.1H NMR (600 MHz, CDCl.sub.3) δ 9.08 (s, 1H), 6.76 (d, J=8.1 Hz, 1H), 6.73-6.68 (m, 2H), 3.77 (s, 3H), 2.93 (t, J=7.5 Hz, 2H), 2.61 (t, J=7.5 Hz, 2H); .sup.13C NMR (150 MHz, CDCl.sub.3) δ 171.8, 155.7, 131.0, 125.1, 116.4, 114.0, 112.6, 55.7, 30.8, 25.8; IR (cm.sup.−1) 3191, 3054, 2934, 1660, 1499, 1240, 793; HRMS (EI) m/z calcd. for C.sub.10H.sub.11NO.sub.2 [M].sup.+: 177.0790. found: 177.0791.

[Example 9] Preparation of 3,4-dihydroquinolin-2(1H)-one (7)

(69) ##STR00064##
White solid (14 mg, 95%); .sup.1H NMR (600 MHz, CDCl.sub.3) δ 9.08 (s, 1H), 7.21-7.09 (m, 2H), 6.98 (t, J=7.3 Hz, 1H), 6.84 (d, J=7.7 Hz, 1H), 2.97 (t, J=7.5 Hz, 2H), 2.65 (t, J=7.5 Hz, 2H); .sup.13C NMR (150 MHz, CDCl.sub.3) δ 172.3, 137.4, 128.0, 127.7, 123.8, 123.2, 115.6, 30.9, 25.5.

[Example 10] Preparation of 6-methyl-3,4-dihydroquinolin-2(1H)-one (8)

(70) ##STR00065##
White solid (14 mg, 88%); m.p. 128-130° C.; 1H NMR (600 MHz, CDCl.sub.3) δ 8.86 (s, 1H), 7.08-6.87 (m, 2H), 6.72 (d, J=8.3 Hz, 1H), 2.92 (t, J=7.5 Hz, 2H), 2.62 (t, J=7.5 Hz, 2H), 2.29 (s, 3H); .sup.13C NMR (150 MHz, CDCl.sub.3) δ 172.1, 134.9, 132.8, 128.7, 128.1, 123.7, 115.5, 30.9, 25.5, 20.9; IR (cm.sup.−1) 3189, 3051, 2918, 1667, 1504, 1373, 812; HRMS (EI) m/z calcd. for C.sub.10H.sub.11NO [M].sup.+: 161.0841. found: 161.0838.

[Example 11] Preparation of 6-chloro-3,4-dihydroquinolin-2(1H)-one (9)

(71) ##STR00066##
White solid (17 mg, 94%); m.p. 158-160° C.; .sup.1H NMR (600 MHz, CDCl.sub.3) δ 9.25 (s, 1H), 7.19-7.08 (m, 2H), 6.77 (d, J=8.0 Hz, 1H), 2.95 (t, J=7.6 Hz, 2H), 2.63 (t, J=7.6 Hz, 2H); .sup.13C NMR (150 MHz, CDCl.sub.3) δ 172.0, 136.1, 128.2, 128.1, 127.6, 125.4, 116.8, 30.5, 25.4; IR (cm.sup.−1) 3193, 3051, 2895, 1669, 1406, 1186, 808; HRMS (EI) m/z calcd. for C.sub.9H.sub.8ClNO [M].sup.+: 181.0294. found: 181.0298.

[Example 12] Preparation of 6-methoxy-4-phenyl-3,4-dihydroquinolin-2(1H)-one (10)

(72) ##STR00067##
White solid (25 mg, 99%); m.p. 122-124° C.; 1H NMR (600 MHz, CDCl.sub.3) δ 9.55 (s, 1H), 7.32 (t, J=7.5 Hz, 2H), 7.28-7.21 (m, 1H), 7.18 (d, J=7.3 Hz, 2H), 6.85 (d, J=8.6 Hz, 1H), 6.72 (d, J=8.6 Hz, 1H), 6.46 (s, 1H), 4.24 (t, J=7.3 Hz, 1H), 3.67 (s, 3H), 2.98-2.83 (m, 2H); .sup.13C NMR (150 MHz, CDCl.sub.3) δ 170.9, 155.9, 141.5, 130.9, 129.1, 128.2, 127.9, 127.4, 116.8, 114.5, 112.9, 55.6, 42.4, 38.5; IR (cm.sup.−1) 3208, 3082, 1681, 1492, 1258, 1096, 701; HRMS (EI) m/z calcd. for C.sub.16H.sub.15NO.sub.2 [M].sup.+: 253.1103. found: 253.1099.

[Example 13] Preparation of 5-methyl-3,4-dihydroquinolin-2(1H)-one (11-A)/8-Methyl-3,4-dihydroquinolin-2(1H)-one (11-B)

(73) White solid (11 mg, 71%); a mixture of two isomers at a ratio of 1.2:1 was obtained.

(74) Major isomer (5-Methyl-3,4-dihydroquinolin-2(1H)-one (11-A)): White solid; m.p. 160-162° C.; .sup.1H NMR (600 MHz, CDCl.sub.3) δ 8.18 (s, 1H), 7.07 (t, J=7.6 Hz, 1H), 6.87 (d, J=7.5 Hz, 1H), 6.63 (d, J=7.8 Hz, 1H), 2.91 (t, J=7.6 Hz, 2H), 2.64 (t, J=7.6 Hz, 2H), 2.29 (s, 3H); .sup.13C NMR (150 MHz, CDCl.sub.3) δ 171.5, 137.3, 136.3, 127.3, 125.2, 122.2, 113.5, 30.5, 22.1, 19.5; IR (cm.sup.−1) 3140, 2915, 1672, 1390, 1218, 766; HRMS (EI) m/z calcd. for C.sub.10H.sub.11NO [M].sup.+: 161.0841. found: 161.0843.

(75) Minor isomer (8-Methyl-3,4-dihydroquinolin-2(1H)-one (11-B)): White solid; m.p. 132-134° C.; .sup.1H NMR (600 MHz, CDCl.sub.3) δ 7.58 (s, 1H), 7.08-7.00 (m, 2H), 6.91 (t, J=7.5 Hz, 1H), 2.96 (t, J=7.5 Hz, 2H), 2.63 (t, J=7.5 Hz, 2H), 2.23 (s, 3H); .sup.13C NMR (150 MHz, CDCl.sub.3) δ 171.6, 135.6, 129.2, 126.0, 123.8, 122.9, 122.8, 30.9, 25.8, 16.8; IR (cm.sup.−1) 3233, 2848, 1659, 1381, 1191, 729; HRMS (EI) m/z calcd. for C.sub.10H.sub.11NO [M].sup.+: 161.0841. found: 161.0839.

[Example 14] Preparation of 4,4-diphenyl-3,4-dihydroquinolin-2(1H)-one (12)

(76) ##STR00068##
White solid (29 mg, 97%); m.p. 253-255° C.; .sup.1H NMR (600 MHz, CDCl.sub.3) δ 8.40 (s, 1H), 7.43-7.17 (m, 7H), 7.11-7.02 (m, 4H), 6.99 (t, J=7.5 Hz, 1H), 6.89-6.78 (m, 2H), 3.40 (s, 2H); .sup.13C NMR (150 MHz, CDCl.sub.3) δ 170.3, 143.8, 137.1, 131.4, 129.6, 128.7, 128.5, 128.3, 127.2, 123.2, 116.3, 52.0, 44.6; IR (cm.sup.−1) 3065, 2911, 1674, 1485, 1372, 757, 697; HRMS (EI) m/z calcd. for C.sub.21H.sub.17NO [M].sup.+: 299.1310. found: 299.1313.

[Example 15] Preparation of 3,4-dihydrobenzo[h]quinolin-2(1H)-one (13)

(77) ##STR00069##
Brown solid (18 mg, 93%); m.p. 193-195° C.; .sup.1H NMR (600 MHz, CDCl.sub.3) δ 8.94 (s, 1H), 7.93 (d, J=8.5 Hz, 1H), 7.84 (d, J=8.1 Hz, 1H), 7.59-7.51 (m, 2H), 7.49 (t, J=7.5 Hz, 1H), 7.30 (d, J=8.2 Hz, 1H), 3.13 (t, J=7.6 Hz, 2H), 2.78 (t, J=7.6 Hz, 2H); .sup.13C NMR (150 MHz, CDCl.sub.3) δ 172.1, 133.2, 132.1, 128.8, 126.6, 126.2, 125.9, 123.1, 122.5, 119.6, 119.4, 31.1, 26.1; IR (cm.sup.−1) 3216, 2928, 1660, 1469, 1392, 816, 758; HRMS (EI) m/z calcd. for C.sub.13H.sub.11NO [M].sup.+: 197.0841. found: 197.0842.

[Example 16] Preparation of 8-bromo-3,4-dihydroquinolin-2(1H)-one (14)

(78) ##STR00070##
White solid (17 mg, 75%); m.p. 77-79° C.; 1H NMR (600 MHz, CDCl.sub.3) δ 7.80 (s, 1H), 7.40 (d, J=8.1 Hz, 1H), 7.12 (d, J=7.3 Hz, 1H), 6.87 (t, J=7.7 Hz, 1H), 2.99 (t, J=7.5 Hz, 2H), 2.64 (t, J=7.5 Hz, 2H); .sup.13C NMR (150 MHz, CDCl.sub.3) δ 170.7, 135.3, 131.0, 127.3, 125.7, 123.9, 109.8, 30.8, 26.1; IR (cm.sup.−1) 3185, 2915, 1674, 1467, 1193, 743; HRMS (EI) m/z calcd. for C.sub.9H.sub.8BrNO [M].sup.+: 224.9789. found: 224.9786.

[Example 17] Preparation of 5-methoxyindolin-2-one (15)

(79) ##STR00071##
White solid (9 mg, 56%); .sup.1H NMR (600 MHz, CD.sub.2Cl.sub.2) δ 8.15 (s, 1H), 6.86 (s, 1H), 6.79 (d, J=8.4 Hz, 1H), 6.75 (d, J=8.4 Hz, 1H), 3.77 (s, 3H), 3.50 (s, 2H); .sup.13C NMR (150 MHz, CDCl.sub.3) δ 176.7, 155.6, 136.0, 126.8, 112.3, 111.7, 109.6, 55.6, 36.5.

[Example 18]Preparation of 6-methoxy-3,4-dihydroquinolin-2(1H)-one (16-A)/8-Methoxy-3,4-dihydroquinolin-2(1H)-one (16-B)

(80) ##STR00072##
White solid (18 mg, 99%); a mixture of two isomers at a ratio of 1.2:1 was obtained.

(81) Major isomer (6-Methoxy-3,4-dihydroquinolin-2(1H)-one (16-A)): White solid; m.p. 140-142° C.; .sup.1H NMR (600 MHz, CDCl.sub.3) δ 9.08 (s, 1H), 6.76 (d, J=8.1 Hz, 1H), 6.73-6.68 (m, 2H), 3.77 (s, 3H), 2.93 (t, J=7.5 Hz, 2H), 2.61 (t, J=7.5 Hz, 2H); .sup.13C NMR (150 MHz, CDCl.sub.3) δ 171.8, 155.7, 131.0, 125.1, 116.4, 114.0, 112.6, 55.7, 30.8, 25.8; IR (cm.sup.−1) 3191, 3054, 2934, 1660, 1499, 1240, 793; HRMS (EI) m/z calcd. for C.sub.10H.sub.11NO.sub.2 [M].sup.+: 177.0790. found: 177.0791.

(82) Minor isomer (8-Methoxy-3,4-dihydroquinolin-2(1H)-one (16-B)): White solid; m.p. 96-98° C.; .sup.1H NMR (400 MHz, CDCl.sub.3) δ 7.78 (s, 1H), 6.94 (t, J=7.9 Hz, 1H), 6.84-6.62 (m, 2H), 3.86 (s, 3H), 2.96 (t, J=7.6 Hz, 2H), 2.64 (t, J=7.6 Hz, 2H); .sup.13C NMR (100 MHz, CDCl.sub.3) δ 170.5, 145.9, 126.6, 124.1, 122.8, 120.1, 109.1, 55.9, 30.8, 25.5; IR (cm.sup.−1) 3204, 2953, 1666, 1377, 1261, 1092, 760; HRMS (EI) m/z calcd. for C.sub.10H.sub.11NO.sub.2 [M].sup.+: 177.0790. found: 177.0788.

[Example 19] Preparation of 6-bromo-3,4-dihydroquinolin-2(1H)-one (17-A)/8-Bromo-3,4-dihydroquinolin-2(1H)-one (17-B)

(83) ##STR00073##
White solid (12 mg, 55%); a mixture of two isomers at a ratio of 2:1 was obtained.

(84) Major isomer (6-Bromo-3,4-dihydroquinolin-2(1H)-one (17-A)): White solid; m.p. 156-158° C.; .sup.1H NMR (600 MHz, CDCl.sub.3) δ 8.41 (s, 1H), 7.33-7.27 (m, 2H), 6.67 (d, J=8.3 Hz, 1H), 2.95 (t, J=7.5 Hz, 2H), 2.59 (t, J=7.5 Hz, 2H); .sup.13C NMR (150 MHz, CDCl.sub.3) δ 171.3, 136.5, 131.0, 130.6, 125.9, 116.9, 115.6, 30.5, 25.3; IR (cm.sup.−1) 3050, 2895, 1669, 1487, 1250, 811, 542; HRMS (EI) m/z calcd. for C.sub.9H.sub.8BrNO [M].sup.+: 224.9789. found: 224.9787.

(85) Minor isomer (8-Bromo-3,4-dihydroquinolin-2(1H)-one (17-B)): White solid; m.p. 77-79° C.; .sup.1H NMR (600 MHz, CDCl.sub.3) δ 7.80 (s, 1H), 7.40 (d, J=8.1 Hz, 1H), 7.12 (d, J=7.3 Hz, 1H), 6.87 (t, J=7.7 Hz, 1H), 2.99 (t, J=7.5 Hz, 2H), 2.64 (t, J=7.5 Hz, 2H); .sup.13C NMR (150 MHz, CDCl.sub.3) δ 170.7, 135.3, 131.0, 127.3, 125.7, 123.9, 109.8, 30.8, 26.1; IR (cm.sup.−1) 3185, 2915, 1674, 1467, 1193, 743; HRMS (EI) m/z calcd. for C.sub.9H.sub.8BrNO [M].sup.+: 224.9789. found: 224.9786.

[Example 20] Preparation of 1-azaspiro[4.5]deca-6,9-diene-2,8-dione (18)

(86) ##STR00074##

(87) An iridium catalyst (Catalyst B, 2.9 mg, 5.0 mol %), sodium tetrakis[3,5-bis(trifluoromethyl)phenyl]borate (4.43 mg, 5.0 mol %), and hexafluoro-2-propanol (1.2 mL) were added to a well-dried vial under an argon atmosphere, stirred for 1 minute, 3-(4-Hydroxyphenethyl)-1,4,2-dioxazol-5-one (0.1 mmol) was added, and the vial was sealed under the argon atmosphere. Thereafter, the reaction mixture was vigorously stirred at 60° C. for 12 hours, cooled to room temperature, filtered with celite, washed with dichloromethane (10 mL×4), and then concentrated under reduced pressure. The concentrated residue was separated and purified with column chromatography (eluent: n-hexane/EtOAc, 2:1 to 1:2) to obtain 1-azaspiro[4.5]deca-6,9-diene-2,8-dione (18).

1-Azaspiro[4.5]deca-6,9-diene-2,8-dione (18)

(88) ##STR00075##
White solid (16 mg, 98%); m.p. 166-158° C.; .sup.1H NMR (600 MHz, acetone-d.sub.6) δ 7.04 (d, J=9.7 Hz, 2H), 6.12 (d, J=9.7 Hz, 2H), 2.45 (t, J=8.0 Hz, 2H), 2.27 (t, J=8.0 Hz, 2H); .sup.13C NMR (150 MHz, acetone-d.sub.6, one carbon merged to others) δ 185.0, 177.0, 151.8, 128.5, 57.9, 32.8; IR (cm.sup.−1) 3246, 1696, 1618, 1247, 859, 682; HRMS (EI) m/z calcd. for C.sub.9H.sub.9NO.sub.2 [M].sup.+: 163.0633. found: 163.0633.

[Example 21] Preparation of 7-methoxy-1-azaspiro[4.5]deca-6,9-diene-2,8-dione (19)

(89) 7-Methoxy-1-azaspiro[4.5]deca-6,9-diene-2,8-dione (19) was prepared in the same manner as in Example 20, except that 3-(4-Hydroxy-3-methoxyphenethyl)-1,4,2-dioxazol-5-one (0.1 mmol) was used as a starting material instead of 3-(4-Hydroxyphenethyl)-1,4,2-dioxazol-5-one.

(90) ##STR00076##
White solid (19 mg, 99%); m.p. 221-223° C.; .sup.1H NMR (600 MHz, CDCl.sub.3) δ 6.84 (d, J=9.9 Hz, 1H), 6.23 (d, J=10.8 Hz, 1H), 6.16 (s, 1H), 5.71 (s, 1H), 3.68 (s, 3H), 2.60-2.52 (m, 2H), 2.38-2.24 (m, 2H); .sup.13C NMR (150 MHz, CDCl.sub.3) δ 180.0, 177.1, 150.8, 150.0, 127.9, 116.7, 59.1, 55.2, 33.6, 29.7; IR (cm.sup.−1) 3301, 1671, 1640, 1395, 1209, 1109, 864; HRMS (EI) m/z calcd. for C.sub.10H.sub.11NO.sub.3 [M].sup.+: 193.0739. found: 193.0739.

[Example 22] Preparation of 7-bromo-1-azaspiro[4.5]deca-6,9-diene-2,8-dione (20)

(91) 7-Bromo-1-azaspiro[4.5]deca-6,9-diene-2,8-dione (20) was prepared in the same manner as in Example 20, except that 3-(3-bromo-4-hydroxyphenethyl)-1,4,2-dioxazol-5-one (0.1 mmol) was used as a starting material instead of 3-(4-hydroxyphenethyl)-1,4,2-dioxazol-5-one.

(92) ##STR00077##
White solid (23 mg, 95%); m.p. 187-189° C.; 1H NMR (600 MHz, CDCl.sub.3) δ 7.29 (s, 1H), 6.86 (d, J=9.9 Hz, 1H), 6.70 (s, 1H), 6.34 (d, J=9.9 Hz, 1H), 2.62-2.47 (m, 2H), 2.37-2.25 (m, 2H); .sup.13C NMR (150 MHz, CDCl.sub.3) δ 177.5, 177.2, 149.7, 149.6, 127.3, 124.9, 60.3, 32.1, 29.3; IR (cm.sup.−1) 3144, 3053, 2854, 1667, 1334, 1098, 798, 665; HRMS (EI) m/z calcd. for C.sub.9H.sub.8BrNO.sub.2 [M+H].sup.+: 241.9817. found: 241.9815.

[Example 23] Preparation of 6-methoxy-1-azaspiro[4.5]deca-6,9-diene-2,8-dione (21)

(93) 6-Methoxy-1-azaspiro[4.5]deca-6,9-diene-2,8-dione (21) was prepared in the same manner as in Example 20, except that 3-(4-hydroxy-2-methoxyphenethyl)-1,4,2-dioxazol-5-one (0.1 mmol) was used as a starting material instead of 3-(4-hydroxyphenethyl)-1,4,2-dioxazol-5-one.

(94) ##STR00078##
White solid (19 mg, 99%); m.p. 179-181° C.; 1H NMR (600 MHz, CDCl.sub.3) δ 6.84 (d, J=9.9 Hz, 1H), 6.23 (d, J=10.8 Hz, 1H), 6.16 (s, 1H), 5.71 (s, 1H), 3.68 (s, 3H), 2.60-2.52 (m, 2H), 2.38-2.24 (m, 2H); .sup.13C NMR (150 MHz, CDCl.sub.3) δ 180.0, 177.1, 150.8, 150.0, 127.9, 116.7, 59.1, 55.2, 33.6, 29.7; IR (cm.sup.−1) 3144, 3067, 2875, 1664, 1224, 855, 511; HRMS (EI) m/z calcd. for C.sub.10H.sub.11NO.sub.3 [M].sup.+: 193.0739. found: 193.0741.

[Example 24] Preparation of 7,9-dimethyl-1-azaspiro[4.5]deca-6,9-diene-2,8-dione (22)

(95) 7,9-Dimethyl-1-azaspiro[4.5]deca-6,9-diene-2,8-dione (22) was prepared in the same manner as in Example 20, except that 3-(4-hydroxy-3,5-dimethylphenethyl)-1,4,2-dioxazol-5-one (0.1 mmol) was used as a starting material instead of 3-(4-hydroxyphenethyl)-1,4,2-dioxazol-5-one.

(96) ##STR00079##
White solid (18 mg, 93%); m.p. 183-185° C.; .sup.1H NMR (600 MHz, CDCl.sub.3) δ 6.57 (s, 2H), 6.52 (s, 1H), 2.51 (t, J=7.8 Hz, 2H), 2.18 (t, J=7.8 Hz, 2H), 1.87 (s, 6H); .sup.13C NMR (150 MHz, CDCl.sub.3) δ 186.0, 177.7, 144.6, 135.2, 57.7, 32.6, 29.8, 16.0; IR (cm.sup.−1) 3194, 2946, 1634, 1341, 902, 761; HRMS (EI) m/z calcd. for C.sub.11H.sub.13NO.sub.2 [M].sup.+: 191.0946. found: 191.0948.

[Example 25] Preparation of 3-(1,3-dioxoisoindolin-2-yl)-1-azaspiro[4.5]deca-6,9-diene-2,8-dione (23)

(97) 3-(1,3-Dioxoisoindolin-2-yl)-1-azaspiro[4.5]deca-6,9-diene-2,8-dione (23) was prepared in the same manner as in Example 20, except that 2-{2-(4-hydroxyphenyl)-1-(5-oxo-1,4,2-dioxazol-3-yl)ethyl}isoindoline-1,3-dione (0.1 mmol) was used as a starting material instead of 3-(4-hydroxyphenethyl)-1,4,2-dioxazol-5-one.

(98) ##STR00080##
White solid (28 mg, 91%); m.p. 260-262° C.; .sup.1H NMR (600 MHz, CDCl.sub.3) δ 7.87 (dd, J=5.0, 2.7 Hz, 2H), 7.77 (dd, J=5.0, 2.7 Hz, 2H), 7.19-7.06 (m, 1H), 7.06-6.88 (m, 1H), 6.58 (s, 1H), 6.37-6.20 (m, 2H), 5.17 (t, J=9.9 Hz, 1H), 2.79-2.69 (m, 1H), 2.64-2.49 (m, 1H); .sup.13C NMR (150 MHz, CDCl.sub.3) δ 184.2, 171.5, 167.4, 149.3, 148.4, 134.7, 131.8, 129.7, 128.8, 123.9, 54.7, 48.3, 35.8; IR (cm.sup.−1) 3353, 1703, 1391, 1117, 860, 714; HRMS (EI) m/z calcd. for C.sub.17H.sub.12N.sub.2O.sub.4 [M].sup.+: 308.0797. found: 308.0801.

[Example 26] Preparation of 8-methoxy-1-azaspiro[4.5]deca-7,9-diene-2,6-dione (24)

(99) 8-Methoxy-1-azaspiro[4.5]deca-7,9-diene-2,6-dione (24) was prepared in the same manner as in Example 20, except that 3-(2-hydroxy-4-methoxyphenethyl)-1,4,2-dioxazol-5-one (0.1 mmol) was used as a starting material instead of 3-(4-hydroxyphenethyl)-1,4,2-dioxazol-5-one.

(100) ##STR00081##
White solid (19 mg, 99%): m.p. 127-129° C.; .sup.1H NMR (600 MHz, CDCl.sub.3) δ 6.38 (d, J=10.0 Hz, 1H), 6.19-6.07 (m, 2H), 5.41 (d, J=2.3 Hz, 1H), 3.79 (s, 3H), 2.75-2.58 (m, 1H), 2.45-2.20 (m, 2H), 2.08-1.95 (m, 1H); .sup.13C NMR (150 MHz, CDCl.sub.3) δ 199.7, 179.6, 170.7, 143.5, 123.1, 97.8, 64.3, 56.3, 32.4, 28.5; IR (cm.sup.−1) 3210, 1673, 1572, 1412, 1206, 995, 633; HRMS (EI) m/z calcd. for C.sub.10H.sub.11NO.sub.3 [M].sup.+: 193.0739. found: 193.0741.

[Example 27] Preparation of 2H-Spiro[naphthalene-1,2′-pyrrolidine]-2,5′-dione (25)

(101) 2H-Spiro[naphthalene-1,2′-pyrrolidine]-2,5′-dione (25) was prepared in the same manner as in Example 20, except that 3-{2-(2-hydroxynaphthalen-1-yl)ethyl}-1,4,2-dioxazol-5-one (0.1 mmol) was used as a starting material instead of 3-(4-hydroxyphenethyl)-1,4,2-dioxazol-5-one.

(102) ##STR00082##
White solid (21 mg, 99%); m.p. 216-218° C.; 1H NMR (600 MHz, CDCl.sub.3) δ 7.61 (d, J=7.7 Hz, 1H), 7.49-7.43 (m, 2H), 7.40-7.33 (m, 2H), 6.20 (d, J=9.9 Hz, 1H), 5.95 (s, 1H), 2.59-2.49 (m, 2H), 2.49-2.39 (m, 1H), 2.09-1.98 (m, 1H); .sup.13C NMR (150 MHz, CDCl.sub.3) δ 200.4, 179.3, 145.4, 143.4, 131.1, 130.1, 129.7, 128.8, 125.6, 123.5, 68.8, 36.7, 28.3; IR (cm.sup.−1) 3167, 3070, 2922, 1672, 1353, 1086, 751; HRMS (EI) m/z calcd. for C.sub.13H.sub.11NO.sub.2 [M].sup.+: 213.0790, found: 213.0792.

[Example 28] Preparation of 1-azaspiro[3.5]nona-5,8-diene-2,7-dione (26)

(103) 1-Azaspiro[3.5]nona-5,8-diene-2,7-dione (26) was prepared in the same manner as in Example 20, except that 3-(4-hydroxybenzyl)-1,4,2-dioxazol-5-one (0.1 mmol) was used as a starting material instead of 3-(4-hydroxyphenethyl)-1,4,2-dioxazol-5-one.

(104) ##STR00083##
White solid (9 mg, 63%); m.p. 158-160° C.; 1H NMR (600 MHz, CDCl.sub.3) δ 6.96 (d, J=9.8 Hz, 2H), 6.58-6.12 (m, 3H), 3.26 (s, 2H); .sup.13C NMR (150 MHz, CDCl.sub.3) δ 184.6, 164.9, 148.2, 130.8, 51.0, 50.1; IR (cm.sup.−1) 3292, 1748, 1661, 1617, 1396, 1260, 866; HRMS (EI) m/z calcd. for C.sub.8H.sub.7NO.sub.2 [M].sup.+: 149.0477. found: 149.0475.

[Example 29] Preparation of Di-Spiroindoline Compound A (27)

(105) Di-spiroindoline compound A (27) was prepared in the same manner as in Example 20, except that 3-{2-(4-methoxy-1H-indol-3-yl) ethyl}-1,4,2-dioxazol-5-one (0.1 mmol) was used as a starting material instead of 3-(4-hydroxyphenethyl)-1,4,2-dioxazol-5-one.

(106) ##STR00084##
Yellow solid (12 mg, 56%); m.p. 286-288° C.; 1H NMR (600 MHz, CDCl.sub.3) δ 6.67 (t, J=8.0 Hz, 2H), 6.07 (d, J=8.2 Hz, 2H), 5.64 (d, J=7.8 Hz, 2H), 5.59 (s, 2H), 3.80 (s, 6H), 2.79-2.67 (m, 2H), 2.53-2.43 (m, 2H), 2.43-2.36 (m, 2H), 2.32-2.22 (m, 2H); .sup.13C NMR (150 MHz, CDCl.sub.3) δ 176.2, 156.0, 150.0, 131.4, 115.0, 103.1, 101.4, 72.8, 65.8, 55.3, 34.2, 30.3; IR (cm.sup.−1) 3272, 2939, 1676, 1608, 1365, 1252, 1083, 728; HRMS (EI) m/z calcd. for C.sub.24H.sub.24N.sub.4O.sub.4 [M].sup.+: 432.1798. found: 432.1801.

[Example 30] Preparation of Di-Spiroindoline Compound B (28)

(107) Di-spiroindoline compound B (28) was prepared in the same manner as in Example 20, except that 3 3-{2-(1-methyl-1H-indol-3-yl)ethyl}-1,4,2-dioxazol-5-one (0.1 mmol) was used as a starting material instead of 3-(4-hydroxyphenethyl)-1,4,2-dioxazol-5-one.

(108) ##STR00085##
Yellow solid (15 mg, 77%); m.p. 204-206° C.; 1H NMR (600 MHz, CDCl.sub.3) δ 7.02 (d, J=7.3 Hz, 2H), 6.94 (t, J=7.6 Hz, 2H), 6.55 (t, J=7.4 Hz, 2H), 5.84 (d, J=7.8 Hz, 2H), 5.57 (s, 2H), 2.88-2.77 (m, 2H), 2.61-2.51 (m, 2H), 2.50-2.41 (m, 2H), 2.36-2.24 (m, 8H); .sup.13C NMR (150 MHz, CDCl.sub.3) δ 176.1, 149.0, 130.0, 129.3, 122.1, 116.8, 105.1, 75.6, 65.4, 34.9, 30.2, 30.0; IR (cm.sup.−1) 3053, 2927, 1686, 1607, 1343, 1226, 729; HRMS (EI) m/z calcd. for C.sub.24H.sub.24N.sub.4O.sub.2 [M].sup.+: 400.1899. found: 400.1899.

Comparative Example 3

(109) 5-Methoxyindolin-2-one was prepared in the same manner as in Example 3, except that Catalyst C was used instead of Catalyst A.

(110) As a result, 5-methoxyindolin-2-one and 7-methoxyindolin-2-one were prepared at 5% or less, respectively.

Comparative Example 4

(111) 5-Methoxyindolin-2-one was prepared in the same manner as in Example 3, except that Catalyst D was used instead of Catalyst A.

(112) As a result, 5-methoxyindolin-2-one was not prepared at all.

(113) The method of preparing a lactam compound according to the Examples of the present invention may produce a lactam compound by using a specific solvent, but in Comparative Examples 3 and 4 using Catalyst C and Catalyst D having different ligands from the catalyst of the present invention, a lactam compound was not prepared.

(114) Therefore, the method of preparing a lactam compound of the present invention using a specific catalyst and a specific starting material may be very useful for preparation of a lactam compound.