Continuous Flow Synthesis and Purification of Atropine with Sequential In-Line Separations of Structurally Similar Impurities

Journal of Flow Chemistry 5(3),133–138, DOI: 10.1556/1846.2015.00013

Flow chemistry has attracted significant interest in pharmaceutical development, where substantial efforts have been directed toward the design of continuous processes. Here, we report a total synthesis of atropine in flow that features an unusual hydroxymethylation and separation of several byproducts with high structural similarity to atropine. Using a combination of careful pH control in three sequential liquid–liquid extractions and afunctionalized resin, atropine is delivered by the flow system with>98% purity