Preparation of alkyl 3-difluoromethyl-1-methyl-1H-pyrazole-4-carboxylic acid ester

摘要

The present disclosure provides a novel and economically advantageous process for preparation of compounds of Formula I, such as alkyl 3-difluoromethyl-1-methyl-1H-pyrazole-4-carboxylic acid ester. The process includes acidification of the sodium enolate of alkyl difluoroacetoacetate by carbonic acid generated in situ by reacting carbon dioxide with water. The disclosure also includes promoting the ring closure reaction in which alkyl 2-alkomethylene-4,4-difluoro-3-oxobutyrate is reacted with methylhydrazine in two phase system with a weak base such as Na2CO3 or K2CO3.

主权项

1. A process for—producing a compound of Formula VI comprising adding carbon dioxide to a compound of Formula V in water to generate carbonic acid in situ and thereby acidifying the compound of Formula V to provide the compound of Formula VI wherein M is sodium, potassium, or lithium; R1 is C1-C6 alkyl; and R2 is CF2H, CFH2, CF3, CCl2H, CClH2, or CCl3.