Simple and Efficient Process for the Large-Scale Preparation of Agomelatine: An Antidepressant Drug

Abstract

A simple and efficient process for the large-scale preparation of agomelatine (1), an antidepressant drug is, described. Agomelatine was prepared in a linear manner starting from readily available, inexpensive 2-naphthol. Key steps in the synthesis are Friedel–Crafts acylation of 2-naphthyl acetate with chloroacetyl chloride, reduction of keto intermediate, and nucleophilic displacement of chloro intermediate with sodium diformylamide. A systemic approach was described to streamline the process into a robust scalable process by controlling the impurities.

GRAPHICAL ABSTRACT

Keywords:

• Agomelatine
• chloro acetylchloride
• Friedel–Crafts acylation
• sodium diformylamide

ACKNOWLEDGMENTS

We thank the management of Dr. Reddy’s Laboratories Ltd. for supporting this work. Cooperation from the project colleagues of API–Analytical Research Department, Integrated Product Development Organization, Dr. Reddy’s Laboratories Ltd., is highly appreciated.

SUPPLEMENTAL MATERIAL

Detailed experimental procedures and spectral characterization data for this article can be accessed on the publisher’s website.