反应详情

温度

0 °C

A mixture of tert-butyl 4-oxopiperidine-1-carboxylate (2 g, 10.04 mmol) and diethyl ether (30 ml) was cooled to 0° C., followed by the dropwise addition of (4-methoxyphenyl)magnesium bromide (0.5 M in diethyl ether, 30 ml, 15 mmol). 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 chromatography eluting with 30:70 ethyl acetate:hexane to provide 3 g tert-butyl 4-hydroxy-4-(4-methoxyphenyl)piperidine-1-carboxylate (100%). LCMS: RT 1.950 min. LCMS (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).

1. temperatureto warm to rt
2. customIt was then slowly quenched with 150 ml of ice cold water
3. extractionthe resulting mixture was extracted with 3×150 ml of DCM
4. customdried
5. filtrationfiltered
6. concentrationconcentrated under vacuum
7. customThe crude product was purified by silica gel chromatography
8. washeluting with 30:70 ethyl acetate