Multigram Synthesis of Fluoroalkyl-Substituted Pyrazole-4-carboxylic Acids

Acylation of tert-butyl 3-(methylamino)but-2-enoate with fluorinated acetic acid anhydrides occurred at the enamine carbon atom. The reaction of the resulting tert-butyl 3-(methylamino)-2-(RFCO)but-2-enoates with alkyl hydrazines resulted in mixtures of isomeric pyrazoles that were easily separated by column chromatography. The target fluorinated pyrazole-4-carboxylic acids were obtained on a multigram scale.