反应详情

温度

0 °C

To a solution of 2-fluoro-3-(3-fluorophenyl)-5-methoxybenzoic acid (402 mg, 1.52 mmol, 1.1 eq) in CH2Cl2 (20 mL) at 0° C. was added oxalylchloride (525 mg, 4.14 mmol, 3.0 eq) and DMF (5 drops). The solution was stirred at 0° C. for 2 h then the solvent removed in vacuo. The residue was taken up in THF (10 mL) and added dropwise to a mixture of 3-amino-2,4-difluorophenol (intermediate X(a)) (200 mg, 1.38 mmol, 1.0 eq) and NaHCO3 (348 mg, 4.14 mmol, 3.0 eq) in THF (10 mL) at 0° C. The mixture was stirred at 0° C. for 4 h then poured into water and extracted with EtOAc. The organic extract was washed with water, brine, dried (Na2SO4) filtered and evaporated in vacuo. The residue was purified by column chromatography (EtOAc:petroleum ether, 0:1 to 1:3) to give the title compound as a white solid (300 mg, 50%).

1. customthe solvent removed in vacuo
2. stirringThe mixture was stirred at 0° C. for 4 h
3. extractionextracted with EtOAc
4. extractionThe organic extract
5. washwas washed with water, brine
6. dry with materialdried (Na2SO4)
7. filtrationfiltered
8. customevaporated in vacuo
9. customThe residue was purified by column chromatography (EtOAc:petroleum ether, 0:1 to 1:3)