反应详情

温度

70 °C

To 5-(3-fluorophenyl)-2-methoxy-3-methyl-benzoic acid (1.09 g, 4.19 mmol, 1.1 eq) was added SOCl2 (10 mL, 12.6 mmol, 3.0 eq). The reaction was heated to 70° C. and stirred for 6 h, then the solvent was removed. The residue obtained was dissolved in THF (10 mL) and added to a mixture of 3-amino-2,4-difluorophenol (intermediate X(a)) (0.405 g, 2.8 mmol, 1.0 eq) and NaHCO3 (1.17 g, 13.9 mmol, 5 eq) in THF (8 mL) at 0° C. The reaction was warmed to room temperature, stirred for 2 h then quenched by addition of water. The aqueous layer was extracted with EtOAc and the combined organic extracts were washed with water and brine dried (Na2SO4) and evaporated in vacuo. The crude residue obtained was purified by column chromatography (petroleum ether:EtOAc 1:0 to 10:1) to give the title compound as a white solid (209 mg, 19%).

1. customthe solvent was removed
2. customThe residue obtained
3. temperatureThe reaction was warmed to room temperature
4. stirringstirred for 2 h
5. customthen quenched by addition of water
6. extractionThe aqueous layer was extracted with EtOAc
7. washthe combined organic extracts were washed with water and brine
8. dry with materialdried (Na2SO4)
9. customevaporated in vacuo
10. customThe crude residue obtained
11. customwas purified by column chromatography (petroleum ether:EtOAc 1:0 to 10:1)