Diethyl Ether → 3-Methyl-1-(2,2,2-trifluoroethyl)-1H-pyrazole-5-carboxylic acid

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Reaction Conditions

Reaction Steps

A mixture of 100 g (0.35 mol) of the trichloromethanesulfonate ester of 2,2,2-trifluoroethanol [J. Med. Chem. 16 1354 (1973)] and 55 g (0.35 mol) of ethyl 3-methylpyrazole-5-carboxylate is heated at 150°-155° C. for two hours. The cooled (70° C.) melt is poured with stirring into 400 ml of ether, 80 ml of conc. ammonium hydroxide, and 150 g ice. The ether layer is separated and distilled to give 48 g bp 100°-110°/11 mm. The ester is stirred under reflux two hours in 175 ml of ethanol and 40 ml of water containing 14 g of potassium hydroxide and evaporated in vacuo. The residue is dissolved in 60 ml of water and acidified with conc. HCl to give 32 g (72%) of 1-(2,2,2-trifluoroethyl)-3-methylpyrazole-5carboxylic acid, mp 135°-139° C.

Provenance & Evidence