反应详情

温度

-78 °C

n-Butyllithium (1.6M in hexane, 42.9 ml, 107.18 mmol) was added dropwise to 1-(benzyloxy)-4-bromobenzene (28.2 g, 107.18 mmol, CAS 6793-92-6) in THF (367 ml) at −78° C. over a period of 15 minutes under nitrogen. The resulting solution was stirred at −78° C. for 1 hour then benzyl 4-oxopiperidine-1-carboxylate (20 g, 85.74 mmol) in THF (122 ml) was added dropwise. The resulting mixture was stirred at −78° C. for 10 minutes, then allowed to warm to room temperature and stirred for 16 hours. The reaction mixture was evaporated to dryness and quenched with saturated ammonium chloride (50 mL), then then extracted with EtOAc (500 mL). The organic layer was dried over MgSO4, filtered and evaporated to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 1 to 100% EtOAc in isohexane. Pure fractions were evaporated to dryness to afford crude product. The crude product was further purified by flash silica chromatography, elution gradient 0 to 3% MeOH in DCM. Pure fractions were evaporated to dryness to afford benzyl 4-[4-(benzyloxy)phenyl]-4-hydroxypiperidine-1-carboxylate (13.49 g, 30.1%) as a gum.

1. stirringThe resulting mixture was stirred at −78° C. for 10 minutes
2. temperatureto warm to room temperature
3. stirringstirred for 16 hours
4. customThe reaction mixture was evaporated to dryness
5. customquenched with saturated ammonium chloride (50 mL)
6. extractionextracted with EtOAc (500 mL)
7. dry with materialThe organic layer was dried over MgSO4
8. filtrationfiltered
9. customevaporated
10. customto afford crude product
11. customThe crude product was purified by flash silica chromatography, elution gradient 1 to 100% EtOAc in isohexane
12. customPure fractions were evaporated to dryness
13. customto afford crude product
14. customThe crude product was further purified by flash silica chromatography, elution gradient 0 to 3% MeOH in DCM
15. customPure fractions were evaporated to dryness