Oxalyl chloride → N-(2,6-difluoro-3-hydroxy-phenyl)-2-fluoro-5-(3-fluorophenyl)-3-methyl-benzamide

Participants

Reaction Conditions

Reaction Steps

To a solution of 2-fluoro-5-(3-fluorophenyl)-3-methyl-benzoic acid (558 mg, 2.25 mmol, 1.0 eq) in DCM (30 mL) at 0° C. was added (COCl)2 (856 mg, 0.57 mL, 6.74 mmol, 3 eq) and DMF (2 drops). The reaction was stirred at 0° C. for 2 h 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-difluorophenol (intermediate X(a)) (330 mg, 2.36 mmol, 1.05 eq) and NaHCO3 (566 mg, 6.74 mmol, 3.0 eq) in THF (30 mL) at 0° C. The reaction was stirred for 3 h at 0° C. then quenched by addition of 1 M HCl 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 (MeOH:DCM, 0:1 to 1:50) to give the title compound as a solid (360 mg, 43%).

Provenance & Evidence