Pyridine, hydrofluoride (1:1) → Benzyl 4-fluoro-4-(hydroxymethyl)piperidine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

To a solution of tert-butyl 4-oxopiperidine-1-carboxylate (7.0 g, 32.8 mmol) in CH2Cl2 (14 mL) at −10° C. was added HF-pyridine (11.6 mL, 82.1 mmol) portionwise. The reaction mixture was stirred for 10 min at −10° C., warmed to RT. After stirring for 16 h, the reaction was quenched with aqueous NaCO3, and extracted with CH2Cl2. The aquoues layer was concentrated to a white paste that was suspended in CH2Cl2 (100 mL). N-benzyloxycarbonyloxysuccinimide (8.2 g, 32.8 mmol) was added and the mixture was stirred at RT for 3 h. The reaction mixture was partitioned between EtOAc and H2O, the organic layer was dried over Na2SO4, filtered and concentrated. Purification on silica gel (10:1 to 1:1 hexanes:EtOAc) gave benzyl 4-fluoro-4-(hydroxymethyl)piperidine-1-carboxylate as a clear oil. M.S. (M+1): 268

Provenance & Evidence