Pyridine → N-Methyl-3,5-difluoromethyl-4-pyrazolecarboxylic acid ethyl ester

BF3.OEt2 (1.24 ml, 10.0 mmol) was added to a solution of TFEDMA (1.20 ml, 10.0 mmol) in dry dichloromethane (10 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 (10 ml). In a second Teflon flask, ethyl 4,4-difluoroacetoacetate (1.03 ml, 10.0 mmol) was added to a solution of pyridine (1.6 ml, 20.0 mmol) in dry acetonitrile (20 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. Methyl hydrazine (0.79 ml, 15.0 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 (10:0-8:2). (10:0 to 8:2). N-Methyl-3,5-difluoromethyl-4-pyrazolecarboxylic acid ethyl ester (1.75 g, 6.89 mmol, 69%) was obtained as a colourless oil, which crystallized when left to stand.

1. customwas removed under reduced pressure
2. additionTo this were added dropwise, at −30° C.
3. customwas brought to room temperature in the cold bath
4. stirringstirred overnight
5. stirringthe mixture was stirred overnight
6. customThe solvent was removed under reduced pressure
7. customthe residue was purified by flash chromatography on silica gel with a pentanes/diethyl ether mixture (10:0-8:2)

ORD record

ord-2e6d78d8826442e69162eed627ae5139

Source dataset

uspto-grants-2016_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09309202B2