Dimethylformamide → 3-(3-Fluorophenyl)-N-(3-hydroxy-2,6-dimethyl-phenyl)-5-methoxy-benzamide

Participants

Reaction Steps

To a solution of 3-(3-fluorophenyl)-5-methoxy-benzoic acid (intermediate III(i)) (1.4 g, 5.7 mmol, 1.0 eq) in CH2Cl2 (15 mL) were added (COCl)2 (2.2 g, 17.3 mmol, 3.0 eq) and DMF (0.01 mL). The reaction mixture was stirred at room temperature for 1.5 h then the solvent and excess reagent removed under reduced pressure. The residue obtained was dissolved in THF (20 mL) and added dropwise to a solution of 3-amino-2,4-dimethylphenol (intermediate X(c)) (791 mg, 5.77 mmol, 1.0 eq) in THF (20 mL) at 0° C. The solution was allowed to warm to room temperature and stirred for 1 h. The reaction mixture was poured into water and extracted with EtOAc. The combined organic extracts were washed with water and brine, 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 (1.2 g, 57%).

Provenance & Evidence