General procedure for the synthesis of 1,4-dimethylpyrazole-5-boronic acid pinacol ester from 1,4-dimethylpyrazole and isopropanol pinacol borate:
1. 1,4-dimethyl-1H-pyrazole (480.0 mg, 4.993 mmol) was dissolved in tetrahydrofuran (20 mL, 300 mmol) at 0 °C and a hexane solution of 1.6 M n-butyllithium (4.7 mL, 7.5 mmol) was slowly added.
2. The reaction solution was stirred at room temperature for 1 hr and then cooled to -78 °C.
3. 2-isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (1.63 mL, 7.99 mmol) was added to the cooled reaction solution.
4. The reaction mixture was stirred at -78 °C for 0.5 h and then slowly warmed to 0 °C (0.5 h).
5. Upon completion of the reaction, the reaction was quenched with saturated saline and extracted with ethyl acetate (3×).
6. The organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure.
7. The residue was purified by fast column chromatography using a gradient elution of ethyl acetate/hexane (0-60%).
8. Purification afforded 142 mg of the target product 1,4-dimethyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole as a white solid.
