PROCESS FOR PREPARING ALKYL 3-DIFLUOROMETHYL-1-METHYL-1H-PYRAZOLE-4-CARBOXYLATE AND ITS ANALOGS

摘要

The disclosure provides a process for the preparation of alkyl 3-difluoromethyl-1-methyl-1H-pyrazole-4-carboxylate and its analogs. The process includes a reaction workup method for Claisen condensation, wherein the enolate salt is acidified after removing remaining starting material and byproducts such as, ethanol and excessive ethyl acetate. The process also includes a method for completely drying alkyl difluoroacetoacetate and its analogs before use in the next step by reacting trialkyl orthoformate with the residual water. The process includes using Na2CO3 and /or K2CO3 to promote the ring-closure reaction to produce the alkyl 3-difluoromethyl-1-methyl-1H-pyrazole-4-carboxylate. The process also includes effectively removing the regioisomer, alkyl 3-difluoromethyl-2-methyl-1H-pyrazole-4-caboxylate formed as a byproduct of the ring closure by a precipitation in a mixed solvent system and thereby eliminating the need for recrystallization of the final product.