反应详情

温度

90 °C

To a solution of 3-bromo-2-fluorobenzonitrile (2.0 g, 10.00 mmol) and 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isoquinoline (2.81 g, 11.00 mmol) in a mixture of DME (30 mL), ethanol (15 mL), and water (15 mL) was added Na2CO3 (4.24 g, 40.0 mmol). This suspension was degassed with a stream of N2 for 10 minutes and then tetrakis(triphenylphosphine)palladium(0) (0.578 g, 0.500 mmol) was added followed by degassing with nitrogen for 10 minutes. The tube was then sealed and heated to 90° C. for 14 hours. The vessel was cooled to room temperature and diluted with EtOAc and water. The mixture was further diluted with brine and extracted three times with EtOAc. The combined organics were dried over MgSO4, filtered, and concentrated to give the crude product as a brown oil. The crude material was purified by flash chromatography on silica using an ISCO machine (80 g SiO2 column, 60 mL/min, 0-20% acetone in CH2Cl2 over 20 minutes, tr=8 minutes) to give the title compound (2.18 g, 8.69 mmol, 87% yield) as a pale yellow solid. ESI MS (M+H)+=249.1.

1. customThis suspension was degassed with a stream of N2 for 10 minutes
2. customby degassing with nitrogen for 10 minutes
3. customThe tube was then sealed
4. temperatureThe vessel was cooled to room temperature
5. additiondiluted with EtOAc and water
6. additionThe mixture was further diluted with brine
7. extractionextracted three times with EtOAc
8. dry with materialThe combined organics were dried over MgSO4
9. filtrationfiltered
10. concentrationconcentrated
11. customto give the crude product as a brown oil
12. customThe crude material was purified by flash chromatography on silica using an ISCO machine (80 g SiO2 column, 60 mL/min, 0-20% acetone in CH2Cl2 over 20 minutes, tr=8 minutes)