2-Chloroanisole → Hexahydro-3-(3-methoxyphenyl)-2H-azepin-2-one

Participants

Reaction Steps

Hexahydro-1-trimethylsilyl-2H-azepin-2-one (9.2 g) in dry tetrahydrofuran (20 ml) was added dropwise with cooling and stirring under a nitrogen atmosphere to a solution of lithium-2,2,6,6-tetramethylpiperidide (prepared from 2,2,6,6-tetramethylpiperidine (8.48 g) and butyl lithium (0.06 mole) in hexane-tetrahydrofuran (38 ml; 10 ml). A further portion of butyl lithium (0.06 mole) in hexane (38 ml) was then added, followed by o-chloroanisole (8.54 g) keeping the reaction temperature between -10° and 5° C. After allowing to warm to room temperature the reaction was stirred for 1.5 hours then decomposed by the addition of water (100 ml). The solvents were removed under reduced pressure, the resulting product partitioned between toluene and 5 M hydrochloric acid. The toluene extracts were dried (MgSO4), the solvent removed and the product distilled affording 2.7 g b.p. 160°-170° C. at 0.1 mm, which yielded 2.6 g of the crystalline title compound from ethyl acetate.

Provenance & Evidence