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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 a functionalized resin, atropine is delivered by the flow system with >98% purity.United States. Defense Advanced Research Projects Agency (DARPA N66001-11-C-4147

Continuous-flow synthesis and purification of atropine with sequential in-line separations of structurally similar impurities