反应详情

To a stirred solution of 3-fluoro-5-(3-fluorophenyl)benzoic acid (533 mg, 2.3 mmol, 1.1 eq) in DCM (10 mL) and DMF (3 drops) at 0° C. was added oxalylchloride (866 mg, 6.8 mmol, 3.3 eq) dropwise. The reaction was warmed to room temperature and stirred for 2 h, and then the solvent removed. The residue that remained was dissolved in THF (6 mL) and added to a solution of 3-amino-2,4-difluoro-phenol (intermediate X(a)) (300 mg, 2.07 mmol, 1.0 eq) and NaHCO3 (868 mg, 10.34 mmol, 5.0 eq) in THF (6 mL) at 0° C. The reaction was warmed to room temperature and stirred for 1 h then quenched by addition of water. The aqueous layer was extracted with EtOAc and the combined organic extracts were washed with 5% Na2CO3, water and brine, dried (Na2SO4), filtered and evaporated in vacuo. The crude residue was recrystallised from DCM: petroleum ether (1:3) and collected by filtration to give the title compound as a solid (390 mg, 52%).

1. customthe solvent removed
2. dissolutionThe residue that remained was dissolved in THF (6 mL)
3. temperatureThe reaction was warmed to room temperature
4. stirringstirred for 1 h
5. customthen quenched by addition of water
6. extractionThe aqueous layer was extracted with EtOAc
7. washthe combined organic extracts were washed with 5% Na2CO3, water and brine
8. dry with materialdried (Na2SO4)
9. filtrationfiltered
10. customevaporated in vacuo
11. customThe crude residue was recrystallised from DCM: petroleum ether (1:3)
12. filtrationcollected by filtration