反应详情

温度

100 °C

Methyl 2-chloroisonicotinate (2.8 g, 16.32 mmol), 2-fluoro-4-(trifluoromethyl)phenylboronic acid (5.09 g, 24.48 mmol), potassium carbonate (1.692 g, 12.24 mmol) and PdCl2 (dppf) (0.354 g, 0.49 mmol) were mixed in methanol (30 mL) in two separate 20 mL microwave vials. The vials were capped and heated at 100° C. for 10 min in a single node microwave reactor. Water and DCM were added and the phases were separated. The water phase (pH 9) was extracted with DCM and the combined organic phase washed with brine, passed through a phase separator and evaporated to yield a dark-orange solid. The solid was dissolved in MTBE and stirred for 15 minutes, then filtered. The orange MTBE layer was treated with hydrogen chloride (4 M in dioxane, 4.08 mL, 16.32 mmol) and stirred for 1 h at room temperature. The precipitate was collected by filtration. Methyl 2-(2-fluoro-4-(trifluoromethyl)phenyl)isonicotinate hydrochloride (5.4 g, 99%) was isolated as a slightly orange solid. MS m/z 300 (M+H)+

1. customseparate 20 mL microwave vials
2. customThe vials were capped
3. additionWater and DCM were added
4. customthe phases were separated
5. extractionThe water phase (pH 9) was extracted with DCM
6. washthe combined organic phase washed with brine
7. customevaporated
8. customto yield a dark-orange solid
9. filtrationfiltered
10. stirringstirred for 1 h at room temperature
11. filtrationThe precipitate was collected by filtration