反应详情

温度

0 °C

4-Hydroxypiperidine (2.41 g, 23.8 mmol), cyclobutanone (5 g, 71.4 mmol) and acetic acid (1.36 ml, 23.8 mmol) were stirred in tetrahydrofuran (35 ml) at 0° C. for 1.5 hours. Sodium triacetoxyborohydride (10.1 g, 47.7 mmol) was then added at 0° C. and the reaction mixture stirred at 0° C. for 1 hour. The mixture was warmed to room temperature and stirred for 1 hour, then heated to 40° C. for 18 hours. The reaction was concentrated in vacuo. The residue was taken up in water (30 ml). The aqueous layer was basified to pH 9 with ammonia and extracted with diethyl ether (3×50 ml). The organics were combined, dried over magnesium sulphate, filtered and concentrated in vacuo. The crude product was purified by flash chromatography on silica gel eluting with dichloromethane:methanol:ammonia (100:0:0 to 93:7:0.7 by volume) to provide the title compound (2.47 g, 67%) as an oil. LRMS APCI+ m/z 156 [MH]+.

1. temperatureThe mixture was warmed to room temperature
2. stirringstirred for 1 hour
3. temperatureheated to 40° C. for 18 hours
4. concentrationThe reaction was concentrated in vacuo
5. extractionextracted with diethyl ether (3×50 ml)
6. dry with materialdried over magnesium sulphate
7. filtrationfiltered
8. concentrationconcentrated in vacuo
9. customThe crude product was purified by flash chromatography on silica gel eluting with dichloromethane:methanol:ammonia (100:0:0 to 93:7:0.7 by volume)