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

Participants

Reaction Conditions

Reaction Steps

To a mixture of 2-fluoro-5-(3-fluorophenyl)benzoic acid (intermediate III(a)) (478 mg, 2.04 mmol, 1.0 eq) and (COCl)2 (777 mg, 6.13 mmol, 3.0 eq) in DCM (20 mL) was added DMF (0.3 mL). The reaction mixture was stirred at 0° C. for 1 h, then the solvent removed in vacuo. The residue obtained was dissolved in THF (20 mL) and added dropwise to a solution of 3-amino-4-chloro-2-fluoro-phenol (intermediate X(d)) (330 mg, 2.04 mmol, 1.0 eq) and NaHCO3 (515 mg, 6.13 mmol, 3.0 eq) in THF (20 mL). After the addition, the reaction mixture was stirred at room temperature for 30 min. The THF was evaporated in vacuo and the aqueous solution adjusted to pH 3 by addition of 1M HCl. The mixture was extracted with EtOAc and the combined organic extracts were dried (Na2SO4), filtered and evaporated in vacuo. The residue was purified by column chromatography (EtOAc:petroleum ether, 0:1 to 1:1) to give the title compound as a yellow solid (200 mg, 26%).

Provenance & Evidence