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Synthesis 2011(1): 79-82  
DOI: 10.1055/s-0030-1258968
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

A Novel Synthesis of the Antidepressant Agomelatine

Christian Markla, Darius P. Zlotos*b
a Institute of Pharmacy and Food Chemistry, Pharmaceutical Chemistry, University of Würzburg, Am Hubland, 97074 Würzburg, Germany
b The German University in Cairo, Department of Pharmaceutical Chemistry, New Cairo City, Al-Tagamoa Al Khames, 11835 Cairo, Egypt
Fax: +20(2)27581041; e-Mail: darius.zlotos@guc.edu.eg ;
Further Information

Publication History

Received 31 August 2010
Publication Date:
09 November 2010 (online)

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Abstract

Agomelatine was synthesized from (2-methoxynaphthalene-8-yl)oxoacetic acid in a four-step approach involving borane reduction, semipinacol rearrangement of the resulting diol, ald­oxime formation, and Ra-Ni hydrogenation/acetylation in 51% overall yield. The reaction sequence includes a novel one-pot conversion of an aldoxime into an N-acetylamine. The synthetic route could be useful as a new approach towards N-acetylarylethyl­amines.

Key words

semipinacol rearrangement - aldoxime reduction - catalytic hydrogenation - acylation - medicinal chemistry

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