Synthesis 2020; 52(18): 2662-2666
DOI: 10.1055/s-0040-1707823
psp
© Georg Thieme Verlag Stuttgart · New York

Environmentally Benign Large-Scale Synthesis of a Precursor to Vortioxetine

Stavroula A. Zisopoulou
a  Department of Chemistry, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece   Email: [email protected]
,
Anastasia E. Pafili
a  Department of Chemistry, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece   Email: [email protected]
,
Petros Gkizis
b  Pharmathen S.A. – R & D API Operations, 9th km Thermi-Thessaloniki, Thessaloniki 57001, Greece
,
Thanos Andreou
b  Pharmathen S.A. – R & D API Operations, 9th km Thermi-Thessaloniki, Thessaloniki 57001, Greece
,
Theoharis V. Koftis
b  Pharmathen S.A. – R & D API Operations, 9th km Thermi-Thessaloniki, Thessaloniki 57001, Greece
,
Alexandra Lithadioti
b  Pharmathen S.A. – R & D API Operations, 9th km Thermi-Thessaloniki, Thessaloniki 57001, Greece
,
Efstratios Neokosmidis
b  Pharmathen S.A. – R & D API Operations, 9th km Thermi-Thessaloniki, Thessaloniki 57001, Greece
,
John K. Gallos
a  Department of Chemistry, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece   Email: [email protected]
› Author Affiliations
This research was co-financed by the European Union and Greek national­ funds through the Operational Program Competitiveness, Entrepreneurship and Innovation, under the call RESEARCH – CREATE – INNOVATE (project code: T1EDK-01161).
Further Information

Publication History

Received: 02 April 2020

Accepted after revision: 06 May 2020

Publication Date:
27 May 2020 (online)


Abstract

An eco-friendly, high-yielding, and transition-metal-free synthesis of 2-[(2,4-dimethylphenyl)thio]aniline precursor to vortioxetine is reported. Vortioxetine, a multi-modal acting drug with high affinity for a range of serotonergic targets, is used for the treatment of major depressive disorder (MDD). The synthesis – applicable in multi-gram scale – involves the reaction of bis(2,4-dimethyl)iodonium bromide with commercial 2-aminophenyl disulfide, whereas its reaction with 2-aminothiophenol afforded the same product but in low to moderate yields. This method works equally well in deep eutectic solvents (DESs), based on choline chloride (ChCl).

Supporting Information

 
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