反应详情

温度

-78 °C

N-(4-Bromophenyl)-1,1,1-trimethyl-N-(trimethylsilyl)silanamine (7 g, 22.12 mmol) in tetrahydrofuran (100 mL) was treated with a solution of n-BuLi (1M, 22 mL) at −78° C. The reaction mixture was stirred an additional hour at −78° C. and then treated with a solution of tert-butyl 4-oxopiperidine-1-carboxylate (3.97 g, 19.91 mmol) in tetrahydrofuran (20 mL). The reaction mixture was stirred at −78° C. for 30 minutes and then warmed to room temperature. The reaction was quenched by addition of saturated ammonium chloride solution (100 mL) and then was extracted with ethyl acetate. The combined organics were washed with water, brine, dried with magnesium sulfate, filtered and concentrated. The crude tert-butyl 4-(4-(bis(trimethylsilyl)amino)phenyl)-4-hydroxypiperidine-1-carboxylate was treated with a solution of tetrabutylammonium fluoride (1M THF, 40 mL) at room temperature for 1 hour. The reaction mixture was diluted with water and extracted with ethyl acetate. The organics were washed with water and brine, dried with magnesium sulfate, filtered and concentrated. Purification by normal phase chromatography provided the title compound.

1. stirringThe reaction mixture was stirred at −78° C. for 30 minutes
2. temperaturewarmed to room temperature
3. customThe reaction was quenched by addition of saturated ammonium chloride solution (100 mL)
4. extractionwas extracted with ethyl acetate
5. washThe combined organics were washed with water, brine
6. dry with materialdried with magnesium sulfate
7. filtrationfiltered
8. concentrationconcentrated
9. additionThe crude tert-butyl 4-(4-(bis(trimethylsilyl)amino)phenyl)-4-hydroxypiperidine-1-carboxylate was treated with a solution of tetrabutylammonium fluoride (1M THF, 40 mL) at room temperature for 1 hour
10. additionThe reaction mixture was diluted with water
11. extractionextracted with ethyl acetate
12. washThe organics were washed with water and brine
13. dry with materialdried with magnesium sulfate
14. filtrationfiltered
15. concentrationconcentrated
16. customPurification by normal phase chromatography