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

Participants

Reaction Steps

To a solution of 5-(3-fluorophenyl)-2-methoxy-3-methyl-benzoic acid (intermediate III(k)) (500 mg, 1.92 mmol, 1.1 eq) in CH2Cl2 (10 mL) was added (COCl)2 (731.6 mg, 5.76 mmol, 3.3 eq) at 0° C. The reaction mixture was allowed to warm to room temperature and stirred for 1 h. The resulting mixture was concentrated under reduced pressure and the residue that remained dissolved in THF (6 mL) and added to a mixture of 3-amino-4-fluoro-2-methylphenol (intermediate X(e)) (246.5 mg, 1.75 mmol, 1.0 eq) and NaHCO3 (733.5 mg, 8.73 mmol, 5.0 eq) in THF (8 mL). After the addition, the reaction mixture was stirred for a further 2 h. Water was added and the aqueous layer extracted with EtOAc. The organic extract was washed with 5% Na2CO3, dried (Na2SO4), filtered and evaporated in vacuo. The residue obtained was purified by column chromatography (petroleum ether: EtOAc, 10:1 to 5:1 then CH2Cl2:MeOH, 20:1) to give the title compound as a white solid (540 mg, 80%).

Provenance & Evidence