反应详情

温度

0 °C

Following the procedure of N. I. Carruthers et al. (J. Med. Chem. 2005, 48, 1857-1872), to a −78° C. solution of 2-bromobenzotrifluoride (12.9 g, 7.8 mL, 57 mmol) in THF (225 mL) was added dropwise a solution of n-BuLi (2.5 M in hexanes, 26 mL, 65 mmol) over 10 min. After 1 h, the reaction mixture was stirred at 0° C. for 10 min, recooled to −78° C., and a solution of N-benzyl-4-piperidone (10.7 g, 57 mmol) in THF (40 mL) was added dropwise via addition funnel over 10 min. After 2 h at −78° C., sat. NH4Cl solution (200 mL) was added and the mixture was warmed to room temperature. The aqueous phase was extracted with EtOAc (2×200 mL). The organic phase washed with H2O (200 mL) and brine (150 mL), dried (MgSO4), and concentrated. Flash chromatography afforded the alcohol (2.7 g), a yellow oil, slightly contaminated with piperidone starting material, in ˜15% yield.

1. customrecooled to −78° C.
2. waitAfter 2 h at −78° C.
3. temperaturethe mixture was warmed to room temperature
4. extractionThe aqueous phase was extracted with EtOAc (2×200 mL)
5. washThe organic phase washed with H2O (200 mL) and brine (150 mL)
6. dry with materialdried (MgSO4)
7. concentrationconcentrated