Efficient Approach to Pure Entacapone and Related Compounds

Abstract

A new and efficient process through a new intermediate, (2E)-2-cyano-3-(3,4-dihydroxy-5-nirtrophenyl)prop-2-enoic acid 15, has been described for preparing substantially pure entacapone 1. This new intermediate 15 was prepared by Knoevenagel condensation of 3,4-dihydroxy-5-nitrobenzaldehyde 2 with 2-cyanoacetic acid 14 and was further condensed with diethylamine to get pure entacapone 1. Some of the important process-related impurities of entacapone (17, 18, 19, and 20) were also prepared easily from this intermediate 15.

GRAPHICAL ABSTRACT

Keywords:

• Aluminum chloride
• cyanoacetic acid
• impurities
• Knoevenagel condensation
• Parkinson's disease
• piperidine

ACKNOWLEDGMENTS

The authors thank the management of Aurobindo Pharma Ltd., Research and Development Centre, for supporting this work. The authors also thank the Analytical Research Department for their valuable contribution.