5-Trifluoromethyl-1H-pyrazole-3-carboxylic acid

Chemical Properties

Synthesis

881693-05-6

129768-28-1

General procedure for the synthesis of 5-trifluoromethylpyrazole-3-carboxylic acid from 1-benzyl-3-(trifluoromethyl)-1H-pyrazole-5-carboxylic acid: liquid ammonia (ca. 50 mL) was condensed into a three-necked flask in an ethanol-dry ice bath, followed by the addition of 1-benzyl-3-(trifluoromethyl)-1H-pyrazole-5-carboxylic acid (100 mg, 3.70 mmol). Sodium metal (about 260 mg, 11.3 mmol) was added to the reaction mixture in batches until the reaction solution showed a persistent blue color for more than 5 minutes. Upon completion of the reaction, the ammonia was allowed to evaporate naturally overnight. Water was added to the residue and acidified with 2N HCl solution to pH < 7. The aqueous phase was extracted twice with ethyl acetate, the organic phases were combined and dried over anhydrous sodium sulfate. The solvent was removed by concentration under reduced pressure to give 5-trifluoromethyl-2H-pyrazole-3-carboxylic acid (560 mg, 3.11 mmol, 84% yield) as a yellow solid with mass spectral data of MS m/z = 179.0 (API-). The product could be used in subsequent reactions without further purification.

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