Methylhydrazine → 1-Methyl-3-(difluoromethyl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxylic acid ethyl ester

(0.34 g, 5 mmol) as a 17% solution in acetonitrile (0.76 ml) was added to a solution of TFEDMA (0.59 ml, 5.0 mmol) in CH3CN (5 ml) under argon in a Teflon flask. The solution was stirred at room temperature for 15 min. In a second Teflon flask, ethyl 4,4,4-trifluoroacetoacetate (0.73 ml, 5.0 mmol) was added to a solution of potassium fluorides (0.88 g, 15.0 mmol) in dry acetonitrile (10 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 (0.32 ml, 6.0 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 (9:1-8:2). N-Methyl-3-difluoromethyl-5-trifluoromethyl-4-pyrazolecarboxylic acid ethyl ester (0.95 g) was obtained as a yellow oil.

1. stirringthe mixture was stirred at room temperature for 15 min
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 (9:1-8:2)

ORD record

ord-b384aaf6c91c4b77ab69f4f207e729d9

Source dataset

uspto-grants-2016_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09309202B2