反应详情

A solution of n-BuLi (2.5 M in hexanes, 1.6 mL, 4.0 mmol) was added dropwise by syringe to a solution of 6-bromo-4-chloro-2-methoxy-3-((6-(trifluoromethyl)pyridin-3-yl)methyl)quinoline (1.711 g, 3.964 mmol, Intermediate 45: step d) in dry THF (20 mL) in a dry ice-acetone bath. After 1-2 minutes, a solution of 2,6-dimethylnicotinaldehyde (0.8 mL, 6.3 mmol) in dry THF (6 mL) was added dropwise. The reaction was stirred for 5 minutes, then was removed from the cold bath and allowed to warm to room temperature. The reaction was quenched with saturated aqueous ammonium chloride. The mixture was partitioned between water and dichloromethane. The separated aqueous phase was further extracted with dichloromethane. The organic phase was dried (Na2SO4), filtered, and concentrated. The crude product was purified by flash column chromatography (silica gel, 0-3% MeOH-DCM) to provide the title compound.

1. customwas removed from the cold bath
2. customThe reaction was quenched with saturated aqueous ammonium chloride
3. customThe mixture was partitioned between water and dichloromethane
4. extractionThe separated aqueous phase was further extracted with dichloromethane
5. dry with materialThe organic phase was dried (Na2SO4)
6. filtrationfiltered
7. concentrationconcentrated
8. customThe crude product was purified by flash column chromatography (silica gel, 0-3% MeOH-DCM)