Pyridine → N-Phenyl-3-difluoromethyl-5-trifluoromethyl-4-pyrazolecarboxylic acid ethyl ester

Participants

Reaction Steps

BF3.OEt2 (2.5 ml, 20.0 mmol) was added to a solution of TFEDMA (2.4 ml, 20.0 mmol) in dry dichloromethane (20 ml) under argon in a Teflon flask. The solution was stirred at room temperature for 15 min, before the dichloromethane was removed under reduced pressure. The residue was then taken up in dry acetonitrile (20 ml). In a second Teflon flask, ethyl 4,4,4-trifluoroacetoacetate (2.8 ml, 20.0 mmol) was added to a solution of pyridine (4.7 g, 60.0 mmol) in dry acetonitrile (40 ml) and the mixture was stirred at room temperature for 15 min. To this were added dropwise, at −30° C., the contents of the first flask. The reaction mixture was brought to room temperature in the cold bath and stirred overnight. Phenyl hydrazine (3.0 ml, 30.0 mmol) was then added dropwise at room temperature and the mixture was stirred overnight. The solvent was removed under reduced pressure and the residue was purified by flash chromatography on silica gel with a pentanes/diethyl ether mixture (9:1). N-Phenyl-3-difluoromethyl-5-trifluoromethyl-4-pyrazolecarboxylic acid ethyl ester (4.47 g, 13.4 mmol, 67%) was isolated as a colourless solid.

Provenance & Evidence