反应详情

温度

0 °C

To a solution of 5-(3-fluorophenyl)-2-methyl-benzoic acid (310 mg, 2.07 mmol, 1.0 eq) in CH2Cl2 (30 mL) at 0° C. was added (COCl)2 (0.52 mL, 6.0 mmol, 3.0 eq) and DMF (2-3 drops). The reaction was stirred at 0° C. for 2 h, and then the solvent was removed in vacuo. The residue was taken up in THF (30 mL) and added to a suspension of 3-amino-2,4-difluoro-phenol (intermediate X(a)) (195.4 mg, 2.07 mmol, 1.0 eq) and NaHCO3 (339.1 mg, 6.2 mmol, 3.0 eq) in THF (70 mL) at 0° C. The reaction was stirred for 3 h at 0° C. then quenched by addition of water and the aqueous layer extracted with EtOAc. The combined organic extracts were washed with brine, dried (Na2SO4), filtered and evaporated in vacuo. The crude residue was purified by chromatography (DCM:MeOH, 1:0 to 20:1) to give the title compound as a solid (230 mg, 48%).

1. customthe solvent was removed in vacuo
2. stirringThe reaction was stirred for 3 h at 0° C.
3. customthen quenched by addition of water
4. extractionthe aqueous layer extracted with EtOAc
5. washThe combined organic extracts were washed with brine
6. dry with materialdried (Na2SO4)
7. filtrationfiltered
8. customevaporated in vacuo
9. customThe crude residue was purified by chromatography (DCM:MeOH, 1:0 to 20:1)