反应详情

温度

140 °C

To Biotage Advancer MW reactor was charged methyl 5-bromo-2′-fluoro-4′-methylbiphenyl-3-carboxylate (20 g, 61.9 mmol), PdCl2(dppf) (0.20 g, 0.273 mmol), potassium vinyl trifluoroborate (12.4 g, 93 mmol), Et3N (13.0 ml, 93 mmol) and EtOH (150 ml). The reactor was sealed and heated at 140° C. for 10 min followed by flash cooling. Removed mixture from the cooling reservoir via vacuum and reaction repeated 5× (120 g, 371 mmol processed). All runs were combined and concentrated to dryness. The crude was partitioned between water and dichloromethane. The layers were separated and the aqueous extracted 2× w/DCM. The combined organic layers were dried over Na2SO4, filtered and concentrated via rotary evaporation to give 116 g amber oil. The crude was purified by automated silica gel chromatography (750 g SiO2, EtOAc/hexanes) to give nearly colorless oil which solidified to white solid upon cooling (99.7 g, 99%).

1. customThe reactor was sealed
2. temperaturecooling
3. customRemoved mixture from the cooling reservoir
4. customvia vacuum and reaction
5. concentrationconcentrated to dryness
6. customThe crude was partitioned between water and dichloromethane
7. customThe layers were separated
8. extractionthe aqueous extracted 2× w/DCM
9. dry with materialThe combined organic layers were dried over Na2SO4
10. filtrationfiltered
11. concentrationconcentrated via rotary evaporation