反应详情

温度

100 °C

Methyl 2-chloroisonicotinate (5 g, 29.14 mmol), 4-(trifluoromethyl)phenylboronic acid (8.30 g, 43.71 mmol), potassium carbonate (6.04 g, 43.71 mmol) and PdCl2 (dppf) (0.633 g, 0.87 mmol) were mixed in methanol (30 mL) in two 20 mL microwave vials. Two drops of water were added to one of the vials and the vials were capped and heated at 100° C. for 10 min in a single node microwave reactor. The solids were removed by filtration and the filtrate evaporated to yield a dark red slurry. DCM and water were added and the phases 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 brown solid. The crude was dissolved in MTBE (180 mL) and solids filtered off. Hydrogen chloride (4 M in dioxane, (7.29 mL, 29.14 mmol) was added dropwise during stirring and a suspension was formed. The suspension was stirred at room temperature for 2.5 h. The solid was collected by filtration and washed with MTBE. MTBE and satd NaHCO3 was added to the solid, the organic phase dried (Na2SO4), filtered and evaporated to yield methyl 2-(4-(trifluoromethyl)phenyl)isonicotinate (5.75 g, 70%) as a beige solid. 1H NMR (400 MHz, cdcl3) δ 4.00 (s, 3H), 7.75 (d, 2H), 7.84 (dd, 1H), 8.18 (d, 2H), 8.33 (s, 1H), 8.87 (dd, 1H). MS m/z 282 (M+H)+

1. customthe vials were capped
2. customThe solids were removed by filtration
3. customthe filtrate evaporated
4. customto yield a dark red slurry
5. customthe phases separated
6. extractionThe water phase (pH 9) was extracted with DCM
7. washthe combined organic phase washed with brine
8. customevaporated
9. customto yield a brown solid
10. filtrationsolids filtered off
11. customa suspension was formed
12. stirringThe suspension was stirred at room temperature for 2.5 h
13. filtrationThe solid was collected by filtration
14. washwashed with MTBE
15. additionwas added to the solid
16. dry with materialthe organic phase dried (Na2SO4)
17. filtrationfiltered
18. customevaporated