反应详情

温度

-78 °C

To a stirred solution of lithium bis(trimethylsilyl)amide (1.0 M in THF, 26.3 mL, 26.3 mmol) in THF (120 mL) at −78° C. was added a cold (−78° C.) solution of 5-(2,3-difluorophenyl)-1-(2,2,2-trifluoroethyl)piperidin-2-one (6.42 g, 21.9 mmol) in THF (100 mL) dropwise, keeping the internal temperature of the reaction mixture below −65° C. The resulting mixture was stirred at −78° C. for 30 min, then a cold (−78° C.) solution of 2,4,6-triisopropylbenzenesulfonyl azide (Harmon et al. (1973) J. Org. Chem. 38, 11-16) (8.81 g, 28.5 mmol) in THF (80 mL) was added dropwise, keeping the internal temperature of the reaction mixture below −65° C. The reaction mixture was stirred at −78° C. for 45 min, then AcOH (6.0 mL, 105 mmol) was added. The resulting mixture was allowed to warm slowly to ambient temperature and was partitioned between saturated aqueous sodium bicarbonate (1 L) and CH2Cl2 (1.5 L). The organic layer was washed with brine, then dried over sodium sulfate, filtered, and concentrated to dryness in vacuo. The crude product was purified by silica gel chromatography, eluting with a gradient of hexanes:EtOAc—100:0 to 40:60, to give the title compound. MS: m/z=334.9 (M+1).

1. customthe internal temperature of the reaction mixture below −65° C
2. customthe internal temperature of the reaction mixture below −65° C
3. stirringThe reaction mixture was stirred at −78° C. for 45 min
4. temperatureto warm slowly to ambient temperature
5. customwas partitioned between saturated aqueous sodium bicarbonate (1 L) and CH2Cl2 (1.5 L)
6. washThe organic layer was washed with brine
7. dry with materialdried over sodium sulfate
8. filtrationfiltered
9. concentrationconcentrated to dryness in vacuo
10. customThe crude product was purified by silica gel chromatography
11. washeluting with a gradient of hexanes