Methanol → Methyl 2,6-dichloro-4-(trifluoromethyl)nicotinate

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Reaction Steps

100 ml of methanol and 4.37 ml (53.9 mmol) of pyridine were cooled in an ice-bath. A solution of 10.0 g (35.9 mmol) of 2,6-dichloro-4-(trifluoromethyl)nicotinoyl chloride [Y. Tsuzuki et al., J. Med. Chem. 47, 2097-2109 (2004)] in 40 ml of dichloromethane was then added dropwise. The mixture was stirred with ice-cooling for one hour and then at room temperature for one hour. The reaction mixture was concentrated on a rotary evaporator. The residue was taken up in ethyl acetate and washed with saturated aqueous sodium bicarbonate solution and then with saturated aqueous sodium chloride solution. The organic phase was dried with magnesium sulfate and the solvent was removed by distillation under reduced pressure. The residue was purified by column chromatography (silica gel: isohexane/ethyl acetate=95/5). This gave 8.98 g (91% of theory) of the target compound.

Provenance & Evidence