Hydrochloric Acid → 5-(4-Chloro-3-methylphenyl)-6-(2,2,2-trifluoroethoxy)nicotinic acid

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Reaction Steps

Methyl 5-(4-chloro-3-methylphenyl)-6-(2,2,2-trifluoroethoxy)nicotinate (example BI; 4.8 g, 13.3 mmol) and LiOH (0.96 g, 40.0 mmol) were combined with THF (70 mL), water (14 mL) and methanol (7 mL) to give a yellow suspension. The reaction mixture was stirred for 22 h at room temperature, 15 mL water was added and the reaction mixture was heated to 45° C. and stirred for 3 h. After cooling to room temperature the reaction mixture was poured into 150 mL of 1 M HCl with ice (pH=1) and extracted with ethyl acetate (2×150 mL). The organic layers were combined, dried with Na2SO4, filtrated and concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 70 g, 0% to 100% EtOAc in heptane to give 3.8 g (82%) of the title compound as a white crystalline solid; MS (ESI): 346.1 (M+H)+.

Provenance & Evidence