反应详情

温度

-10 °C

Combine a solution of lithium aluminum hydride (42 mL, 1 M in THF, 42.0 mmol). Cool to about −10° C. using an isopropyl alcohol/ice bath. Slowly add a solution of sulfuric acid (1.15 mL, 21.6 mmol) in tetrahydrofuran (4 mL) at such a rate that the reaction temperature does not rise above −10° C. Stir vigorously and warm to ambient temperature. After 2 hours, add a solution of 3-(3,4-dichlorophenyl)-3-(2-(t-butyldimethylsilyloxy)ethyl)-6-oxopiperidine (5.56 g, 13.85 mmol) in tetrahydrofuran (12 mL). Heat to reflux. After 18 hours, add 1/1 tetrahydrofuran/water. After 1 hour, filter and rinse with dichloromethane. Suspend the solids removed by filtration in tetrahydrofuran (400 mL). To the tetrahydrofuran suspension add water (20 mL) and 15% aqueous sodium hydroxide solution (8 mL) and stir vigorously. After 2 hours, filter. Combine the filtrates and concentrate in vacuo to give an aqueous suspension. Extract twice with dichloromethane. Dry the organic layers over Na2SO4, filter, and concentrate in vacuo to give the title compound.

1. customdoes not rise above −10° C
2. temperaturewarm to ambient temperature
3. temperatureHeat to reflux
4. waitAfter 18 hours
5. waitAfter 1 hour
6. filtrationfilter
7. washrinse with dichloromethane
8. customremoved by filtration in tetrahydrofuran (400 mL)
9. additionTo the tetrahydrofuran suspension add water (20 mL) and 15% aqueous sodium hydroxide solution (8 mL)
10. stirringstir vigorously
11. waitAfter 2 hours
12. filtrationfilter
13. concentrationconcentrate in vacuo
14. customto give an aqueous suspension
15. extractionExtract twice with dichloromethane
16. dry with materialDry the organic layers over Na2SO4
17. filtrationfilter
18. concentrationconcentrate in vacuo