1-METHYL-3-TRIFLUOROMETHYLPYRAZOLE-5-BORONIC ACID

154471-65-5

344591-91-9

The general procedure for the synthesis of (1-methyl-3-trifluoromethyl-1H-pyrazol-5-yl)boronic acid from 1-methyl-3-trifluoromethyl-1H-pyrazole was as follows: 1-methyl-3-trifluoromethyl-1H-pyrazole (1.00 g, 6.66 mmol) was dissolved in THF (25 mL) in an oven-dried, round-bottomed flask. The flask was cooled to -78°C in an acetone/dry ice bath. Under stirring, 2.5 M n-butyllithium/hexane solution (3.196 ml, 7.99 mmol) was slowly added dropwise to the solution, followed by triisopropyl borate (5.01 g, 26.64 mmol). The reaction mixture was gradually warmed to room temperature and stirred continuously for 3 hours. Upon completion of the reaction, the pH of the reaction mixture was adjusted to 6 with 1N HCl solution, followed by removal of THF under vacuum.The aqueous phase was extracted with EtOAc (3 x 100 ml). The organic phases were combined, washed with brine and dried with anhydrous MgSO4. After filtration, the solvent was evaporated to give 2-methyl-5-trifluoromethyl-2H-pyrazole-3-boronic acid (1.12 g, 5.80 mmol, 87% yield) as a white solid. The product was analyzed by LCMS, m/z (%) = 195 (M+H, 100). 1H NMR (400 MHz, DMSO-d6) δ: 8.37-8.40 (m, 2H), 7.57 (dd, J=4.0 Hz, 1H), 4.06 (s, 3H).