The general procedure for the synthesis of (1,3,5-trimethyl-1H-pyrazol-4-yl)boronic acid from 4-bromo-1,3,5-trimethylpyrazole was as follows: to a dry flask was added 300 mg (1.59 mmol) of 4-bromo-1,3,5-trimethylpyrazole and 4.0 mL of THF. The mixture was cooled to -78°C, and 1 equivalent of n BuLi (1.6 M in hexane). After stirring the reaction mixture for 1.5 hours, 0.19 mL (1.08 equiv) of trimethyl borate was added. Stirring was continued for 2 hr while allowing the reaction bath temperature to slowly increase to -10°C. Subsequently, 1.5 mL of 5N HCl was added and stirring was continued for 30 min. Upon completion of the reaction, the aqueous layer was extracted three times with ethyl acetate. The organic phases were combined, dried with anhydrous MgSO4, filtered and concentrated under reduced pressure to an oil. The oil was dissolved in a solvent mixture of methanol/dichloromethane and concentrated again under reduced pressure. The residue was ground with acetone/ethyl acetate mixed solvent and filtered to give (1,3,5-trimethyl-1H-pyrazol-4-yl)boronic acid as a white solid in a yield of 92.1 mg (37.6% yield).1H-NMR (DMSO-d6) δ: 5.92 (s, 1H), 3.72 (s, 3H), 2.34 (s, 3H), 2.26 (s, 3H ) ppm.
