Dimethylformamide → 4,4-Difluoro-4-(4'-methoxy-biphenyl-4-yl)-butyric Acid

Participants

Reaction Steps

2,2-Difluoro-N-methoxy-2-(4′-methoxy-biphenyl-4-yl)-N-methyl-acetamide. To a solution of difluoro-(4′-methoxy-biphenyl-4-yl)-acetic acid (3.74 g, 13.4 mmol) in dichloromethane (40 mL) and acetonitrile (40 mL) is added oxalyl chloride (2.40 mL, 27.5 mmol) followed by N,N-dimethylformamide (1.05 mL, 13.6 mmol). This mixture is stirred at room temperature for 45 min and added over 10 min to a solution of N,O-dimethylhydroxylamine hydrochloride (5.23 g, 53.6 mmol) and triethylamine (11.2 mL, 80.4 mmol) in t-butanol (40 mL), THF (80 mL), and water (30 mL) at 0° C. The resulting mixture is stirred for 4 hours while warming from 0° C. to room temperature. The reaction is diluted with water and the layers separated. The organic layer is washed in succession with saturated aqueous NaHCO3 and brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude product is purified by column chromatography (silica gel, 20-30% EtOAc/hexanes) to give the desired product as a pale yellow solid.

Provenance & Evidence