Oxalyl chloride → N-(6-Fluoro-3-hydroxy-2-methyl-phenyl)-3-(3-fluorophenyl)-5-methy-benzamide

Participants

Reaction Steps

To a solution of 3-(3-fluorophenyl)-5-methyl-benzoic acid (448 mg, 1.95 mmol, 1.1 eq) in CH2Cl2 (10 mL) was added (COCl)2 (742 mg, 5.85 mmol, 3.3 eq) and DMF (3 drops) at 0° C. The reaction mixture was stirred at room temperature for 1.5 h. The resulting mixture was concentrated in vacuo to remove the solvent and excess reagent. The solid obtained was dissolved in THF (10 mL) and added dropwise to a mixture of 3-amino-4-fluoro-2-methylphenol (intermediate X(e)) (250 mg, 1.77 mmol, 1.0 eq) and NaHCO3 (744 mg, 8.86 mmol, 5.0 eq) in THF (15 mL) at 0° C. The reaction was allowed to warm to room temperature and stirred for 1 h. Water was added and the aqueous layer extracted with EtOAc. The organic extract was washed with water and brine, dried (Na2SO4), filtered and evaporated in vacuo. The residue obtained was purified by column chromatography (CH2Cl2:MeOH, 500:1 to 300:1) to give the title compound as a white solid (396 mg, 63%).

Provenance & Evidence