Dimethyl Fumarate: Heterogeneous Catalysis for the Development of an Innovative Flow Synthesis

Abstract

The present work describes the development of an improved synthesis of the active pharmaceutical ingredient (API) dimethyl fumarate. The use of continuous flow technology and the newly developed methylation conditions solve some of the issues of previous commercial production strategies, e.g., reaching complete conversion and avoiding the formation of toxic impurities. The optimization was carried out using the design of experiment approach and afforded a very efficient, sustainable process, suitable for the industrial application.

Practical Aspects Concerning Catalysis with Molecularly Doped Metals**

“…A proxy for industry's activities in the field are publications in the leading organic process journal ( Organic Process Research & Development ). From enzymatic stereoselective reactions with heterogenized enzymes, [39] through the acid‐catalyzed synthesis of valued dimethyl fumarate over silica‐supported propylsulfonic acid, [40] researchers from fine chemical, pharmaceutical, and flavor and fragrance companies regularly report findings concerning the use of heterogeneous catalysts to produce valued fine chemicals. Almost invariably, the solid catalysts are used under continuous flow conditions.…”