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With n-butyllithium In tetrahydrofuran; hexane |
2 Hexahydro-3-(3-methoxyphenyl)-1-methyl-2H-azepin-2-one
EXAMPLE 2 Hexahydro-3-(3-methoxyphenyl)-1-methyl-2H-azepin-2-one A solution of butyl lithium (0.05 mole) in hexane (34.4 ml), was treated with 2,2,6,6-tetramethylpiperidine (9.3 ml) followed by dry THF (100 ml) under an inert atmosphere at 0° C. The mixture was treated with N-methylcaprolactam (6.9 ml, 55 mM) and stirred for 30 minutes. A solution of butyl lithium (0.05 mole) in hexane (34.4 ml) was added, the reaction mixture stirred 15 minutes then treated with o-chloroanisole (3.1 ml). After 30 minutes a solution of butyl lithium (0.05 moles) in hexane (31.25 ml) was added, the mixture stirred for 15 minutes and treated with o-chloroanisole (3.1 ml). After a further 30 minutes, the reaction was quenched with water (100 ml) and the solvents removed under reduced pressure. The residue was partitioned between 5 N HCl (100 ml) and toluene (250 ml). The organic phase was washed with brine, dried and the solvents removed under reduced pressure. Distillation of the residue gave crude title compound (5.4 g) b.p. 150°/0.5 mm. Recrystallisation from diisopropyl ether gave pure material (4.2 g), m.p. 74°-75° C. identical with authentic material. |
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With hydrogenchloride; n-butyllithium In tetrahydrofuran; hexane; toluene |
3 Hexahydro-3-(3-methoxyphenyl)-1-methyl-2H-azepin-2-one
EXAMPLE 3 Hexahydro-3-(3-methoxyphenyl)-1-methyl-2H-azepin-2-one A solution of butyl lithium (0.05 moles) in hexane (31.25 ml), was treated with 2,2,6,6-tetramethylpiperidine (8.5 ml), followed by THF (100 ml) under an inert atmosphere at 0° C. A solution of N-methylcaprolactam (6.25 ml, 50 mM) in THF (20 ml) was added, the mixture stirred for 30 minutes and treated with a solution of butyl lithium (0.05 mole) in hexane (31.25 ml). After 15 minutes, o-chloroanisole (6.2 ml) was added and the mixture stirred for fifteen hours at ambient temperature. The reaction was quenched with water (100 ml), the solvents removed in vacuo and the residue partitioned beteen 5 N HCl (100 ml) and toluene (250 ml). The organic phase was washed with brine, dried and the solvents removed under reduced pressure. Distillation of the residue gave crude title compound (40%) b.p. about 140°/0.05 mm. Recrystallisation from isopropyl ether gave pure material (31%), m.p. 74°-75° C., identical with authentic material. |
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With n-butyllithium In tetrahydrofuran; hexane |
4.A Step A
Step A Preparation of 3-(3-methoxy-phenyl)-1-methyl-azepan-2-one To 1.6 M n-BuLi in hexane (31.3 mL, 50 mmol) at 0° C. was added a solution of 2,2,6,6-tetramethyl piperidine (8.43 mL, 50 mmol) in anh. THF (100 mL) over 5 min. N-methylcaprolactam (6.41 mL, 50 mmol) in anhydrous THF (20 mL) was added. After stirring the reaction mixture for 10 min, a further portion of 1.6M n-BuLi in hexane (31.3 mL, 50 mmol) was added, the mixture was stirred for 10 min, and 2-chloroanisole (6.34 mL, 50 mmol) was added. After stirring for 30 min under Ar, the reaction was quenched with H2O, stirred for 30 min, concentrated in vacuo, diluted with EtOAc and washed with 5N HCl (100 mL) and brine. The organic layer was dried (MgSO4), concentrated and purified using SiO2 chromatography (10% EtOAc/CH2Cl2) to give the title compound. |
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