1029716-44-6

269410-08-4

General procedure for the synthesis of 4-pyrazole boronic acid pinacol ester from 1-(1-ethoxyethyl)-4-pyrazoleboronic acid pinacol ester: 1-(1-ethoxyethyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (60.00 g, 224 mmol) was mixed with cyclopentyl methyl ether (CPME. 120 mL) and 2,3-dimethyl-2,3-butanediol (26.49 g, 224 mmol) were mixed. The reaction mixture was cooled to 5-10 °C, then a solution of anhydrous hydroquinone (HQ) in CPME (3.1 M, 86.8 mL, 269 mmol) was slowly added over 15 min, followed by additional CPME (15 mL). The reaction mixture was stirred at 20-25 °C and the progress of the reaction was monitored by TLC.After 7 h, additional hydrochloric acid solution (3 mL, 9.3 mmol) was added to the reaction mixture and stirring was continued for 15 h to afford 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole hydrochloride, which did not require isolation. The temperature of the reaction mixture was raised to 20°C after addition of additional hydrochloric acid solution within 10 min. Additional CPME (10 mL) was added and the reaction mixture was stirred for 15 min and then cooled in an ice bath.After 3 h, the reaction mixture was filtered and the solid (triethylamine hydrochloride) was washed with cold CPME (3 x 60 mL). The filtrate and washings were combined to give 426 g of a solution containing 102.3 mg of 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole. The solution (8.15 g in total, 94% yield) was used directly in the next step.