Sodium borohydride → Tert-butyl 3-fluoro-4-hydroxypiperidine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

tert-Butyl 3-fluoro-4-oxopiperidine-1-carboxylate [van Niel, M. B.; et al.; J. Med: Chem. 1999, 42, 2087-2104] (52.27 g, 241 mmol) was dissolved in anhydrous MeOH (600 mL), cooled to 0° C. and treated in portions with sodium borohydride (37.8 g, 361 mmol) over a 15 minute period. After stirring at 0° C. for 30 minutes, the mixture was stirred at ambient temperature for 4 hours. The mixture was concentrated under reduced pressure and the residue was partitioned between saturated ammonium chloride solution (400 mL) and EtOAc (400 mL). The aqueous layer was extracted with EtOAc and the combined organic extracts were washed with brine (200 mL), dried over Na2SO4, filtered and concentrated to provide the desired product as a thick oil that slowly solidified upon standing (52.7 g).

Provenance & Evidence