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calculated to be 52.3% (72.2% w/w).
Conclusions
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In summary, we have described the synthesis of ago-
melatine, an important API with great potential for the
treatment of major depression, by using a widely applicable
key starting material, 7-methoxy-1-tetralone (1). Our syn-
thesis is among the most efficient in terms of overall yield
and cost effectiveness and is well suited for large industrial
production. The experimental conditions are mild and envi-
ronmentally friendly. In addition, common and easily ac-
cessible chemicals are involved, while the most expensive of
those, namely DDQ, was used only in catalytic amounts.
Efforts for further optimization of the synthetic process are
currently underway.
Supporting Information (see footnote on the first page of this arti-
cle): Full experimental details for the preparation and copies of the
1H and 13C NMR spectra of compounds 6, 7, 12, 13, and synthetic
agomelatine are provided.
Acknowledgments
The authors are grateful to Dr. Thanos Andreou for fruitful dis-
cussions, especially concerning the catalytic oxidation of chloride 6
to the corresponding aromatic chloride 12.
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Received: July 8, 2014
Published Online: September 8, 2014
Eur. J. Org. Chem. 2014, 6376–6379
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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