反应详情

温度

80 °C

Method 1—Step c 2-(3-Bromo-phenyl)-1-methyl-1H-benzoimidazole (0.85 g, 2.96 mmol), (S)-(+)-Nipecotic acid ethyl ester (0.60 g, 3.85 mmol) and cesium carbonate (4.82 g, 14.80 mmol) were placed into a dry Schlenk tube under nitrogen. At the same time palladium acetate (0.14 g, 0.60 mmol), and rac-2,2′bis(diphenylphosphino)-1,1′-binaphtyl (BINAP) (0.57 g, 0.90 mmol) were placed into a dry 7 mL vial under nitrogen. Then dry toluene (5 mL) was added and the mixture was stirred 20 minutes under nitrogen before being added to the first flask. The reaction mixture was heated at 80° C. overnight, cooled to room temperature, filtered off, and the insoluble material was washed with EtOAC (3×10 mL). The organic solution was concentrated under reduced pressure and crude was purified by flash chromatography (eluent: cyclohexane:AcOEt gradient from 100% of cyclohexane to cyclohexane 4:AcOEt 1) to afford 0.75 g of the title compound (70%).

1. additionbefore being added to the first flask
2. temperaturecooled to room temperature
3. filtrationfiltered off
4. washthe insoluble material was washed with EtOAC (3×10 mL)
5. concentrationThe organic solution was concentrated under reduced pressure and crude
6. customwas purified by flash chromatography (eluent: cyclohexane:AcOEt gradient from 100% of cyclohexane to cyclohexane 4:AcOEt 1)