The Synthesis of Warfarin Using a Reconfigurable‐Reactor Platform Integrated to a Multiple‐Variable Optimization Tool

Optimization of the asymmetric synthesis of warfarin, an important anticoagulant, has been evaluated using a reconfigurable reaction platform capable of performing batch, continuous flow, and plug‐flow synthesis. Further, this platform has been integrated with a novel, multidimensional, multiple variable analysis tool that can evaluate multiple critical quality attributes (CQA), percent conversion and enantiomeric excess in this case, from a single injection that is repeatedly recycled in a closed loop of chromatography columns, a detector and a heart‐cut valve. Further, the new, integrated analysis system also facilitates validation of each QA, providing a high‐level of confidence in analytical measurements, which are obtained without operator intervention.