Synlett 2012; 23(15): 2279-2283
DOI: 10.1055/s-0031-1290456
letter
© Georg Thieme Verlag Stuttgart · New York

100 Gram Scale Synthesis of a Key Intermediate of Matrix Metalloproteinase Inhibitor in a Continuous-Flow System Based on a Copper-Free Sonogashira Reaction Using an Ionic Liquid as a Catalyst Support

Takahide Fukuyama*
a   Department of Chemistry, Graduate School of Science, Osaka Prefecture University, Sakai, Osaka 599-8531, Japan
,
Md. Taifur Rahman
a   Department of Chemistry, Graduate School of Science, Osaka Prefecture University, Sakai, Osaka 599-8531, Japan
,
Yukihito Sumino
b   Quality, Safety and Regulatory Affairs Management Division, SHIONOGI & Co., LTD., Osaka, Osaka 541-0045, Japan, Fax: +81(72)2549695   eMail: fukuyama@c.s.osakafu-u.ac.jp
,
Ilhyong Ryu*
a   Department of Chemistry, Graduate School of Science, Osaka Prefecture University, Sakai, Osaka 599-8531, Japan
› Institutsangaben
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Publikationsverlauf

Received: 30. Mai 2012

Accepted after revision: 28. Juni 2012

Publikationsdatum:
14. August 2012 (online)


Abstract

The key intermediate of matrix metalloproteinase (MMP) inhibitor was synthesized using a flow microreactor for a copper-free Sonogashira coupling reaction in an ionic liquid. The ionic liquid [emim]NTf2 was used as a solvent and a catalyst support. A 100 g scale synthesis was achieved in combination with a flow-extraction/catalyst-recycling system, in which the ionic liquid containing the palladium catalyst was continuously recycled.