Ethyl Acetate → Tert-butyl 8-oxa-4-azabicyclo[5.1.0]octane-4-carboxylate

Participants

Reaction Steps

To a stirred solution of 16.4 g 2,3,6,7-tetrahydro-azepine-1-carboxylic acid tert-butyl ester in 420 ml dichloromethane was added at −60° C. 35.8 g m-chloroperbenzoic acid (70% purity). The mixture was allowed to slowly warm to room temperature overnight, 1 l ethylacetate was added and the solution was extracted with aqueous sodium bicarbonate, 1N aqueous sodium hydroxide and brine. Evaporation of the solvent and chromatography yielded 14.5 g (82%) 8-oxa-4-aza-bicyclo[5.1.0]octane-4-carboxylic acid tert-butyl ester as colorless liquid; MS (EI): m/e=213 (M+,5%), 158 (22%), 140 (12%), 57 (100%). To a solution of 14.3 g 8-oxa-4-aza-bicyclo[5.1.0]octane-4-carboxylic acid tert-butyl ester in 750 ethanol was added 150 ml water, 35.8 g ammonium chloride and 43.6 g sodium azide. The mixture was stirred at 75° C. over night, the solvents were greatly removed by distillation under vacuum and the residue was suspended in ethanol and filtered. The ethanol was distilled off and the residue was suspended in ethylacetate and filtered. Removal of the solvent and chromatography on silicagel with ethylacetate/hexane 1:1, yielded 13.5 g (79%) 4-azido-5-hydroxy-azepane-1-carboxylic acid tert-butyl ester as a viscous oil; MS (ISP): m/e=257 (M+H+).

Provenance & Evidence