反应详情

温度

80 °C

Method 9—Step a 2-(5-Bromo-2-fluoro-phenyl)-5-methoxy-benzoimidazole-1-carboxylic acid tert-butyl ester (obtained as described in general method 6, step c) (1.05 g, 2.50 mmol), piperidine-4-carboxylic acid ethyl ester (0.51 g, 3.25 mmol) and cesium carbonate (4.07 g, 12.50 mmol) were placed into a dried schlenk tube and 3 cycles of vacuum/nitrogen were performed, then dry toluene (4 mL) was added. At the same time palladium(II)acetate (0.11 g, 0.50 mmol), and BINAP (0.48 g, 0.75 mmol) were placed into a dried schlenk tube under nitrogen and 3 cycles of vacuum/nitrogen were performed. Then dry toluene (2 mL) was added, at room temperature under nitrogen, and the mixture was added to the first schlenk. The reaction mixture was heated at 80° C. overnight, cooled to room temperature, EtOAC (20 mL) was added and the mixture filtered off. Solvent was removed and the crude was purified by flash chromatography (eluent gradient: cyclohexane:EtOAc from 4:1 to 3:1), to obtain 0.82 g of the title compound (69%).

1. additionthe mixture was added to the first schlenk
2. temperaturecooled to room temperature
3. additionEtOAC (20 mL) was added
4. filtrationthe mixture filtered off
5. customSolvent was removed
6. customthe crude was purified by flash chromatography (eluent gradient: cyclohexane:EtOAc from 4:1 to 3:1)