反应详情

温度

0 °C

To a solution of (1R,2R)-1-{2-[2-(3-Benzyloxy-4-methoxy-phenyl)ethoxy]cyclohexyl}-2,5-dioxopyrrolidin-3-(R)-yl acetate (42.0 g, 84.8 mmol) in anhydrous THF (300 mL) at 0° C. was added borane-THF complex solution (1.0 M, 297 mL, 3.5 mol equivalents) under N2 via an addition funnel over a period of 60 minutes. The reaction mixture was heated to reflux for 60 minutes. The reaction mixture was cooled to 0° C. and quenched slowly by addition of methanol (˜15 mL). The reaction mixture was concentrated under reduced pressure to remove the THF and to the residue was added methanolic-HCl solution (˜1.25 M in methanol, 297 mL, 3.5 equivalents). The solution was then heated at 70-80° C. for 2 hours. The reaction mixture was cooled to ambient temperature and concentrated under reduced pressure to give (3R)-1-[(1R,2R)-2-[2-(3-benzyloxy-4-methoxy-phenyl)ethoxy]cyclohexyl]-3-pyrrolidinol hydrochloride as a colorless syrup (35.0 g, 89% yield). The sample was used directly without further purification in the next step.

1. temperatureThe reaction mixture was heated
2. temperatureto reflux for 60 minutes
3. customquenched slowly by addition of methanol (˜15 mL)
4. concentrationThe reaction mixture was concentrated under reduced pressure
5. customto remove the THF
6. temperatureThe solution was then heated at 70-80° C. for 2 hours
7. temperatureThe reaction mixture was cooled to ambient temperature
8. concentrationconcentrated under reduced pressure