306960-77-0

White to pale yellow solid

2-(Trifluoromethyl)pyrimidine-5-carboxylic acid is used as pharmaceutical intermediate.

General procedure for the synthesis of 2-(trifluoromethyl)pyrimidine-5-carboxylic acid from ethyl 2-(trifluoromethyl)pyrimidine-5-carboxylate: To a 1 M aqueous lithium hydroxide solution (380 mL, 379.3 mmol) was added a solution of ethyl 2-(trifluoromethyl)pyrimidine-5-carboxylate (56.8 g, 252.8 mmol) dissolved in tetrahydrofuran (THF, 500 mL). The reaction mixture was stirred at room temperature for 16 hours. After completion of the reaction, it was concentrated under vacuum to remove the organic solvent. The remaining aqueous solution was acidified with concentrated hydrochloric acid to pH 1. The resulting precipitate was collected by vacuum filtration to afford 44.4 g (91% yield) of 2-trifluoromethylpyrimidine-5-carboxylic acid as an off-white powder. The product was confirmed by 1H NMR (500 MHz, DMSO-d6): δ 9.44 (s, 2H). retention time (Rt) = 0.81 min by LCMS (Analytical Method A), and mass spectra (ESI negative ion mode): m/z = 190.9 ([M-H]-).

[1] Patent: WO2016/91776, 2016, A1. Location in patent: Page/Page column 362; 363
[2] Journal of medicinal chemistry, 2000, vol. 43, # 21, p. 3995 - 4004
[3] Patent: US2009/131431, 2009, A1. Location in patent: Page/Page column 148
[4] Patent: WO2007/36733, 2007, A1. Location in patent: Page/Page column 223