反应详情

温度

-50 °C

To a solution of 9.8 mL (24 mmole) butyllithium (2.5 M solution in hexane) in diethylether (20 mL) under N. at −78° C. was slowly added 2-bromo-5-fluoroanisole (5.0 g, 24 mmole) in diethylether (5 mL). The mixture was allowed to warm up to −50° C. At this point, 1-benzyl-4-piperidone (4.62 g, 24.4 mmole) in diethylether (3 mL) was added. The resulting mixture was allowed to stirred at −50° C. for 30 minutes, and then warmed to room temperature. The reaction was quenched by dropwise addition of saturated NH4Cl solution. The mixture was then transferred to a separatory funnel, the layers were separated and the aqueous was extracted three times with EtOAc. The combined organic phase was dried over Na2SO4, filtered and concentrated. Flash chromatography (elution with 7:3 EtOAc-hexanes) afforded 5.27 g (68%) of 1-benzyl-4-(5-fluoro-2-methoxy-phenyl)-4-hydroxypiperidine as a yellow oil.

1. customat −78° C.
2. temperaturewarmed to room temperature
3. customThe reaction was quenched by dropwise addition of saturated NH4Cl solution
4. customThe mixture was then transferred to a separatory funnel
5. customthe layers were separated
6. extractionthe aqueous was extracted three times with EtOAc
7. dry with materialThe combined organic phase was dried over Na2SO4
8. filtrationfiltered
9. concentrationconcentrated
10. washFlash chromatography (elution with 7:3 EtOAc-hexanes)