Pyridine → 3-(Difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid

Temperature

60 °C

To a solution of 1,1,2,2-tetrafluoroethyldimethylamine (3.2 g, 22 mmol) in diethyl ether (10 ml) and dioxane (10 ml) was added dropwise, under a nitrogen atmosphere, at a temperature of from 0 to 5° C., a solution of BF3-etherate (49% BF3, 5.6 ml, 44 mmol). After the addition had ended, the reaction mixture was stirred for 5 min. Subsequently, pyridine (1.7 g, 22 mmol) and a solution of ethyl 3-ethoxyacrylate (2.9 g, 20 mmol) in dioxane (2 ml) were added dropwise successively to the reaction mixture at a temperature of from 0 to 5° C. After stirring at room temperature for 6 hours, the reaction mixture was added at a temperature of from 0 to 5° C. to a mixture of sodium hydroxide (4.4 g, 110 mmol) and methylhydrazine (1.4 g, 30 mmol) in water (75 ml) and then stirred at room temperature for 1 h. Subsequently, the reaction mixture was heated to 60° C. and stirred at this temperature for 0.5 h. The reaction mixture was freed of volatile constituents. The resulting residue was taken up in water (50 ml), washed with ethyl acetate and then brought to a pH of 2 with conc. hydrochloric acid. The precipitated solid was isolated by filtration, washed with water and dried under reduced pressure at a temperature of 50° C. Isomerically pure 3-difluoromethyl-1-methylpyrazole-4-carboxylic acid was obtained in a yield of 50%.

1. additionAfter the addition
2. stirringAfter stirring at room temperature for 6 hours
3. stirringstirred at room temperature for 1 h
4. stirringstirred at this temperature for 0.5 h
5. washwashed with ethyl acetate
6. customThe precipitated solid was isolated by filtration
7. washwashed with water
8. customdried under reduced pressure at a temperature of 50° C

ORD record

ord-7f499c8f3a5c4351adc5e2353184fbad

Source dataset

uspto-grants-2012_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08188295B2