Synthesis of the antimalarial API artemether in a flow reactor

The earlier developed flow protocol for stoichiometric reduction of an important biologically derivedpharmaceutical precursor, artemisinin, to dihydroartemisinin was extended to a sequential reaction toproduce one of the final APIs, artemether. A highly active heterogeneous catalyst was found for theetherification reaction. The use of QuadraSil catalyst allows to eliminate one step of reaction workup. Acomparative Life Cycle Assessment of both reactions has shown advantages of the flow process over theoptimized literature batch protocols. Results of LCA highlight the significance of solvents in pharmaceut-icals manufacture and the advantage of flow technology, enabling small solvent inventories to be used.