Acetic Acid → Tert-butyl 4-cyclohexyl-4-hydroxypiperidine-1-carboxylate

Participants

Reaction Steps

Anhydrous cerium(III) chloride (10.0 g) was added to THF (100 ml) with stirring under ice-cooling and a mixture was stirred at ambient temperature overnight and then cooled in an ice bath. A solution of cyclohexyl magnesium chloride (2M solution in diethyl ether) (20.3 ml) was dropwise added to the mixture with stirring on ice bath (keeping the temperature below 6° C.). To the mixture was added dropwise a solution of tert-butyl 4-oxo-1-piperidinecarboxylate (5.38 g) in THF (25 ml) and the mixture was stirred at 0-6° C. for 1 hour. 10% aqueous acetic acid (100 ml) was added to the reaction mixture and extracted twice with ethyl acetate (100 ml). The extracts were collected, washed with saturated aqueous sodium chloride, dried over magnesium sulfate and evaporated in vacuo. The resulting residue was chromatographed on silica gel (400 ml) eluting with a mixture of n-hexane and ethyl acetate (2:1 v/v). The fractions containing the desired compound were collected and evaporated under reduced pressure to give tert-butyl 4-cyclohexyl-4-hydroxy-1-piperidinecarboxylate (7.27 g).

Provenance & Evidence