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

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.

1. temperaturecooling for one hour
2. concentrationThe reaction mixture was concentrated on a rotary evaporator
3. washwashed with saturated aqueous sodium bicarbonate solution
4. dry with materialThe organic phase was dried with magnesium sulfate
5. customthe solvent was removed by distillation under reduced pressure
6. customThe residue was purified by column chromatography (silica gel: isohexane/ethyl acetate=95/5)

ORD record

ord-0a65addbe34646d285fd3e1620ecc4a1

Source dataset

uspto-grants-2012_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08143411B2