From Flow Chemistry in the Lab Towards Industrial Implementation on Scale – Case Studies on Continuous API Synthesis
Oliver Kappe,
Professor,
Karl Franzens University of Graz
Continuous flow processes form the basis of the petrochemical and bulk chemicals industry where strong competition, stringent environmental and safety regulations, and low profit margins drive the need for highly performing, cost effective, safe and atom efficient chemical operations. In contrast to the commodity chemical industry, however, the fine chemical industry primarily relies on its existing infrastructure of multipurpose batch or semi-batch reactors. Fine chemicals, such as drug substances and active pharmaceutical ingredients (APIs), are generally considerably more complex than commodity chemicals and usually require numerous, widely diverse reaction steps for their synthesis. These requirements generally make versatile and reconfigurable multipurpose batch reactors the technology of choice for their preparation. However, the advantages of continuous flow processing are increasingly being appreciated also by the pharmaceutical industry and, thus, a growing number of scientists, from research chemists in academia to process chemists and chemical engineers in pharmaceutical companies, are now starting to employ continuous flow technologies on a more routine basis. In this lecture, contributions from our research group in the field of continuous flow processing will be highlighted. Emphasis will be given to highly atom efficient and process intensified chemical transformations useful for the synthesis of APIs or key intermediates that are often too hazardous to be executed in a batch reactor. These involve azide, diazomethane and nitration chemistry, selective precious metal-free olefin and nitrogroup reductions, oxidation reactions involving pure oxygen, and flow photochemistry applications. Special emphasis will be given to the scalability issues and industrial collaboration with both pharma companies and CMOs and equipment/technology providers.
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