Potassium Carbonate → 2-Fluoro-N-(6-fluoro-3-hydroxy-2-methyl-phenyl)-3-(3-fluorophenyl)-5-methyl-benzamide

Participants

Reaction Steps

To a solution of 2-fluoro-3-(3-fluorophenyl)-5-methyl-benzoic acid (intermediate III(e)) (580 mg, 2.3 mmol, 1.1 eq) in CH2Cl2 (10 mL) at 0° C., was added oxalyl chloride (812 mg, 6.4 mmol, 3 eq) dropwise. DMF (10 drops) was added and the mixture was stirred at room temperature for 3 h. The organic solvent and excess reagent were removed under reduced pressure. The residue that remained was dissolved in THF (10 mL) and added dropwise to a mixture of 3-amino-4-fluoro-2-methylphenol (intermediate X(e)) (300 mg, 2.1 mmol, 1 eq) and K2CO3 (1.47 g, 10.6 mmol, 5 eq) in THF (20 mL) at 0° C. After addition was completed, the reaction was allowed to warm to room temperature and stirred for 3 h. The resulting mixture was poured into water and extracted with EtOAc. The combined organic extracts were washed with brine, dried (Na2SO4), filtered and evaporated in vacuo. The residue obtained was purified by column chromatography (petroleum ether:EtOAc, 100:1 to 10:1) to give the title compound as a white solid (200 mg, 25%).

Provenance & Evidence