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; Md. Taifur Rahman; Yukihito Sumino; Ilhyong Ryu

doi:10.1055/s-0031-1290456

Synlett, Table of Contents

Synlett 2012; 23(15): 2279-2283
DOI: 10.1055/s-0031-1290456

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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*

^aDepartment of Chemistry, Graduate School of Science, Osaka Prefecture University, Sakai, Osaka 599-8531, Japan

,

Md. Taifur Rahman

^aDepartment of Chemistry, Graduate School of Science, Osaka Prefecture University, Sakai, Osaka 599-8531, Japan

,

Yukihito Sumino

^bQuality, 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*

^aDepartment of Chemistry, Graduate School of Science, Osaka Prefecture University, Sakai, Osaka 599-8531, Japan

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Abstract

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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.

Key words

microreactor - flow reaction - ionic liquids - palladium - Sonogashira coupling - matrix metalloproteinase inhibitor

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References

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