tert-Butyl 4-oxopiperidine-1-carboxylate → Tert-butyl 4-hydroxy-4-(4-methoxyphenyl)piperidine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

A mixture of commercial tert-butyl 4-oxopiperidine-1-carboxylate (2.0 g, 10.0 mmol) and diethyl ether (30 ml) was cooled to 0° C. To this mixture was added dropwise a solution of (4-methoxyphenyl)magnesium bromide (0.5 M in diethyl ether, 30 ml, 15 mmol). After complete addition, the reaction mixture was allowed to warm to rt and stirred for 2 h. It was then slowly quenched with 150 ml of ice cold water and then the resulting mixture was extracted with 3×150 ml of DCM. The organic layers were combined, dried, filtered, and concentrated under vacuum. The crude product was purified by silica gel column chromatography (30:70 ethyl acetate:hexane) to provide the desired product (3.0 g, 100% yield): LC-MS (ES-API): m/z 305.5 (M−H)+; 1H NMR (400 MHz, DMSO-d6) δ 7.37 (q, J=1.0 Hz, 2H), 6.86 (q, J=1.0 Hz, 2H), 4.94 (s, 1H), 3.82 (d, J=11.5 Hz, 2H), 3.73 (s, 3H), 3.13 (br. s, 2H), 1.75 (td, J=12.9, 4.8 Hz, 2H), 1.56 (d, J=12.3 Hz, 2H), 1.41 (s, 9H).

Provenance & Evidence