反应详情

温度

-78 °C

n-Butyl lithium (1.6M in hexanes, 6.50 mL, 10.39 mmol) was added dropwise to 5-bromo-2-chloropyridine (2.0 g, 10.39 mmol) in ether (30 mL) cooled to −78° C. over a period of 15 minutes. The resulting solution was stirred at −78° C. for 45 minutes then a solution of tert-butyl 4-oxo-1-piperidinecarboxylate (1.66 g, 8.31 mmol) in ether (10 mL) was added dropwise. The reaction was allowed to warm slowly to room temperature then quenched with ammonium chloride solution (50 mL) and extracted with EtOAc. The extract was washed sequentially with water and saturated brine, dried over MgSO4 and concentrated by evaporation, then purified by flash silica chromatography, elution gradient 20 to 50% EtOAc in isohexane. Pure fractions were evaporated to dryness to afford tert-butyl 4-(6-chloropyridin-3-yl)-4-hydroxypiperidine-1-carboxylate (1.33 g, 41%) as a cream solid.

1. temperatureto warm slowly to room temperature
2. customthen quenched with ammonium chloride solution (50 mL)
3. extractionextracted with EtOAc
4. washThe extract was washed sequentially with water and saturated brine
5. dry with materialdried over MgSO4
6. concentrationconcentrated by evaporation
7. custompurified by flash silica chromatography, elution gradient 20 to 50% EtOAc in isohexane
8. customPure fractions were evaporated to dryness