Background and overview of the preparation method of 1-methyl-1H-pyrazole-4-boronic acid
1-Methyl-1H-pyrazole-4-boronic acid is an organic intermediate, which can be prepared from 1-methyl-4-bromopyrazole as raw material by reacting with triisopropyl borate. 1-Methyl-1H-pyrazole-4-boronic acid can react with pinacol to give 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxola Boran-2-yl)-1H-pyrazole, this compound is an important chemical intermediate.
The preparation method of 1-methyl-1H-pyrazole-4-boronic acid is reported
(1) Take 580L of tetrahydrofuran with a purity of 99.9% and a moisture of 0.1% and vacuum pump it into a 1000L stainless steel cryogenic reactor with a jacketed stainless steel coil with a motor power of 5.5KW and a rotation speed of 80 rpm. , then pump 80kg of 1-methyl-4-bromopyrazole with a purity of 98.0% into the cryogenic kettle, start stirring for 20 minutes to mix evenly; replace the reaction kettle with nitrogen 3 times to ensure that there is no oxygen, the following operation process Stirring is always on and cannot be stopped; then, the inner coil is passed into liquid nitrogen, the reactant is cooled to -80~-70℃, and maintained at -80~-70℃, slowly add 163.68kg of 2.5M n-butyllithium dropwise, and control The dripping speed is completed at about 8h25min. If the dripping speed is too fast, the temperature is difficult to control, the dropping speed is too slow, and the reaction time is too long, impurities that cannot be removed will be produced, and the product yield will be low and the purity will be reduced;
(2) Keep the temperature at -80~-70℃, continue to drop 103.4kg of 98.0% triisopropyl borate, control the dripping speed for 1h30min, and continue the reaction at this temperature for 2h;
(3) After the reaction mixture was heated to -15°C, it was neutralized with 150 ml of 15% ammonium chloride aqueous solution. The mixture was warmed to room temperature and heated to room temperature. Stir for 1 hour. The organic layer was separated and the aqueous layer was extracted with 100 ml THF. The combined organic and aqueous layers were dried over Na2SO4 and the solvent was evaporated. under reduced pressure. The residue was washed with diethyl ether (2 x 50 ml) and dried in vacuo to give methyltetrahydrofuran as white 1-methyl-1H-pyrazole-4-boronic acid.
References
[1] [Chinese invention] CN201811103323.8 Preparation method of pyrazole compounds
[2] Ivachtchenko A V , Kravchenko D V , Zheludeva V I , et al. Synthesis of Pinacol Esters of 1‐Alkyl‐1H‐pyrazol‐5‐yl‐ and 1‐Alkyl‐1H‐pyrazol‐4‐ylboronic Acids.[J]. ChemInform, 2005, 36.
