tert-Butyl 4-oxopiperidine-1-carboxylate → tert-Butyl 4-(3-fluoro-4-methoxyphenyl)-4-hydroxypiperidine-1-carboxylate

Participants

Reaction Steps

A stirred solution of tert-butyl 4-oxopiperidine-1-carboxylate (4.5 g, 22.6 mmol) in diethyl ether (100 mL) at 0° C. was treated with a solution of (3-fluoro-4-methoxyphenyl)magnesium bromide (49.7 mL, 24.8 mmol, 0.5 M in tetrahydrofuran). The reaction mixture was allowed to warm to rt and was stirred at for 12 h. It was then diluted with 100 mL water and the layers were separated. The aqueous layer was extracted three times with 150 mL of ethyl acetate and the combined organic layers were dried over anhydrous sodium sulfate, filtered, and evaporated. The residue was purified by silica gel chromatography (120 g column) eluting with 30% ethyl acetate in petroleum ether to obtain 6.5 g of tert-butyl 4-(3-fluoro-4-methoxyphenyl)-4-hydroxypiperidine-1-carboxylate as a clear liquid; 1H NMR (400 MHz, DMSO-d6) δ ppm 1.33-1.47 (m, 11H) 1.52-1.61 (m, 2H) 1.69-1.84 (m, 2H) 3.03-3.22 (m, 2H) 3.77-3.89 (m, 6H) 5.09 (s, 1H) 7.10 (s, 1H) 7.17-7.26 (m, 1H) 7.25-7.33 (m, 1H).

Provenance & Evidence