Hydrochloric Acid → 1-(Diphenylmethyl)azetidin-3-one

Participants

Reaction Conditions

Reaction Steps

A solution of oxalyl chloride (1.92 mL) in methylene chloride (70 mL) was cooled to −74° C. under nitrogen-gas atmosphere and thereto was added dropwise dimethylsulfoxide (3.22 mL) over a period of 15 minutes. The mixture was stirred at the same temperature for 20 minutes and thereto was added dropwise a solution of 1-benzhydryl-3-hydroxyazetidine (5 g) in methylene chloride (25 mL) over a period of 45 minutes. The mixture was stirred at the same temperature for 75 minutes. Thereto was added dropwise triethylamine (11.6 mL) over a period of 20 minutes and the mixture was stirred at the same temperature for 150 minutes. The reaction mixture was warmed to 0° C. and thereto was added dropwise an aqueous 1N HCl solution (64 mL). The mixture was stirred at room temperature and the aqueous layer was separated. To the organic layer was added an aqueous 1N HCl solution. The mixture was stirred and the aqueous layer was separated (said extraction procedure was repeated three times). The combined aqueous layer was neutralized (pH 9) with an aqueous 2N sodium hydroxide solution under stirring and extracted with ethyl acetate. The extract was washed with a brine, dried over magnesium sulfate and filtered. The filtrate was concentrated in vacuo and the resultant crude product was purified by column chromatography on silica gel (solvent: hexane/ethyl acetate=100/0 to 90/10) to obtain 1-benzhydrylazetidin-3-one (4.57 g, Yield: 92%) as a white solid.

Provenance & Evidence