tert-Butyl 3-hydroxy-4-phenylpiperidine-1-carboxylate

Synthesis

100-59-4

161157-50-2

1000931-04-3

The general procedure for the synthesis of N-BOC-3-hydroxy-4-phenylpiperidine from phenylmagnesium chloride and tert-butyl 7-oxa-3-azabicyclo[4.1.0]heptane-3-carboxylate was as follows: referring to the method of Tetrahedron Lett., 1979, 17, 1503, to a stirred tetrahydrofuran (THF, 3 mL) solution of phenylmagnesium chloride (0.753 mL, 1.51 mmol) and copper(I) iodide (0.0191 g, 0.100 mmol) solution of tetrahydrofuran (THF, 3 mL), a THF (1 mL) solution of tert-butyl 7-oxa-3-azabicyclo[4.1.0]heptane-3-carboxylate (0.200 g, 1.00 mmol) was slowly added. The reaction mixture was gradually warmed to room temperature and stirred continuously for 16 hours. Upon completion of the reaction, the reaction was quenched with saturated aqueous ammonium chloride solution, followed by extraction of the mixture with ethyl acetate (AcOEt). The organic layers were combined, dried with anhydrous sodium sulfate, filtered and concentrated in vacuum to afford tert-butyl 3-hydroxy-4-phenylpiperidine-1-carboxylate (0.261 g, 94% yield) as an oil. The product was characterized by 1H NMR (400 MHz, DMSO-d6): δ 1.49 (s, 9H), 1.76 (m, 3H), 2.50-2.78 (m, 3H), 3.70 (m, 1H), 4.30 (bd, 1H), 7.30 (m, 5H).

References