Non-Infringing Efficient One-Pot Process for the Preparation of Pure Entacapone

Abstract

A new and non-infringing efficient one-pot process for the preparation of catechol-O- methyltransferase (COMT) enzyme inhibitors, entacapone 1 under mild condition, initially reaction of 3-methoxy-4-hydroxy-5-nitro-benzaldehyde 5 with 2-cyano acetic acid 13 in presence of new organic base benzyl Trimethyl ammonium hydroxide, i.e. Triton-B which undergo Knoevenagel condensation to get intermediate 22 which is then react with SOCl₂ to get chloride intermediate 23 and which undergo condensation with diethylamine to get 6 and finally deprotection in presence of HBr-AcOH to get economically efficient and industrially feasible entacapone 1 with higher purity and yield without isolation of any intermediate as compared to conventional batch wise process.

Graphical Abstract

Keywords:

• benzyl trimethyl ammonium hydroxide
• cyano acetic acid
• Knoevenagel condensation
• Parkinson’s disease
• one-pot process
• industrially feasible

Correction Statement

This article has been corrected with minor changes. These changes do not impact the academic content of the article.

Acknowledgments

The authors are thankful to the Department of Chemistry, Shri Chhatrapati Shivaji Mahavidyalaya, Shrigonda for providing a research facility for laboratory work and also thankful to the research advisory committee for funding.

Disclosure statement

No potential conflict of interest was reported by the authors.