反应详情

温度

85 °C

Methyl 4-chloronicotinate (20 g, 117 mmol), (4-chloro-2-fluorophenyl)boronic acid (22.4 g, 128 mmol), Pd(Ph3P)4 (9.4 g, 8.16 mmol) and Cs2CO3 (114 g, 350 mmol) were taken in a solvent mixture of 1,4-dioxane (400 mL) and water (30 mL) and purged with nitrogen for 5 min and heated to 85° C. After overnight stirring at this temperature the reaction mixture was diluted with ethyl acetate and filtered through a bed of diatomaceous earth (Celite®). The bed was further washed with ethyl acetate. Combined filtrate was washed with water (1×100 mL), dried (Na2SO4) and concentrated under reduced pressure to afford the crude product which was purified via combi flash (gradient of methanol and chloroform) to afford methyl 4-(4-chloro-2-fluorophenyl)nicotinate (13 g, 48.9 mmol, 42%, with purity of 77% by LC/MS) as a brown solid. LC/MS (ESI) m/e 266.0 [(M+H)+, calcd for C13H10ClFNO2 266.1]; LC/MS retention time (method B): tR=1.69 min.

1. custompurged with nitrogen for 5 min
2. additionwas diluted with ethyl acetate
3. filtrationfiltered through a bed of diatomaceous earth (Celite®)
4. washThe bed was further washed with ethyl acetate
5. washCombined filtrate was washed with water (1×100 mL)
6. dry with materialdried (Na2SO4)
7. concentrationconcentrated under reduced pressure
8. customto afford the crude product which
9. customwas purified via combi flash (gradient of methanol and chloroform)