Synthesis
The general procedure for the synthesis of 1-methyl-5-(trifluoromethyl)-1H-pyrazole-4-carboxylic acid from ethyl 1-methyl-5-(trifluoromethyl)-1H-pyrazole-4-carboxylate is as follows:
Preparation of intermediate 65b: Ethyl 1-methyl-5-(trifluoromethyl)pyrazole-4-carboxylate (2.91 g, 13.0 mmol) was dissolved in THF (52 mL) and cooled to 0 °C. Subsequently, a solution of lithium hydroxide (627 mg, 26.1 mmol) in water (26 mL) was slowly added. The reaction mixture was stirred overnight at room temperature. After completion of the reaction, the mixture was acidified to pH 1-2 with 1 M HCl and extracted with EtOAc (4 x 50 mL). The organic layers were combined, washed with brine (50 mL), dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to afford 1-methyl-5-(trifluoromethyl)pyrazole-4-carboxylic acid (2.39 g, 12.33 mmol, 94% yield) as an off-white solid.
The product characterization data are as follows:
1H NMR (CDCl3, 400 MHz) δ/ppm: 8.02 (1H, s), 4.13 (3H, q, J = 2.0 Hz) Exchangeable protons.
19F NMR (CDCl3, 400 MHz) δ/ppm: -57.2.
MS Method 2: RT: 1.16 min, m/z 193.0 [M-H]-.
