tert-Butyl 4-oxopiperidine-1-carboxylate → Tert-butyl 4-hydroxypiperidine-1-carboxylate

Participants

Reaction Steps

A solution of tert-butyl 4-oxo-1-piperidinecarboxylate (179.24 g, 899.62 mmol) in anhydrous methanol (1.5 L) at 0° C. under a nitrogen atmosphere was treated with sodium borohydride (34.03 g, 899.62 mmol). Sodium borohydride was added portion-wise (5 g every 10 minutes). The ice bath was removed 20 minutes after the last addition of sodium borohydride, and the reaction mixture stirred for 72 hours. To the reaction solution, 1 N sodium hydroxide aqueous solution (1 L) was added, and allowed to stir for 2 hours. The organic layer was removed under reduced pressure, and anhydrous diethyl ether (200 mL) was added. The aqueous layer was extracted with anhydrous diethyl ether (1.5 L). The organic layers were combined, washed with brine, dried over magnesium sulfate, filtered and evaporated under reduced pressure to give a yellow oil. The product was further dried under high vacuum to remove residual solvent to give 177.04 g (97%) of tert-butyl 4-hydroxy-1-piperidinecarboxylate as a white solid. 1H NMR (DMSO-d6, 400 MHz) δ 4.688(s, 1H), 3.678-3.589(m, 3H), 2.940(m, 2H), 1.689-1.646(m, 2H), 1.385(s, 9H), 1.252-1.212(m, 2H).

Provenance & Evidence