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

Participants

Reaction Steps

To a solution of 2-fluoro-5-(3-fluorophenyl)-3-methyl-benzoic acid (intermediate III(f)) (528 mg, 2.1 mmol, 1.0 eq), in CH2Cl2 (20 mL) and DMF (3 drops) was added (COCl)2 (0.5 mL). The reaction was stirred at room temperature for 1 h then the solvent and excess reagent were removed under reduced pressure. The residue obtained was dissolved in THF (20 mL) and added to a mixture of 3-amino-4-fluoro-2-methylphenol (intermediate X(e)) (300 mg, 2.1 mmol, 1.0 eq) and NaHCO3 (536 mg, 6.38 mmol, 3 eq) in THF (20 mL) at 0° C. After addition was completed, the reaction mixture was stirred at room temperature for 30 min. Water was added and the aqueous phase was adjusted to pH 3 by addition of diluted HCl. The aqueous solution was extracted with EtOAc and the combined organic extracts were dried (Na2SO4), filtered and evaporated in vacuo. The residue obtained was purified by column chromatography (petroleum ether:EtOAc, 100:1 to 1:1) to give the title compound as a white solid (420 mg, 53%).

Provenance & Evidence