An Adaptive Auto‐Synthesizer using Online PAT Feedback to Flexibly Perform a Multistep Reaction

Automated chemical synthesizers have become more common in recent years but struggle to apply rigid procedures broad substrate scopes. We developed an adaptive auto-synthesizer that uses online HPLC and FTIR measurements adapt the changing reactivities of different substrates, allowing precise control reaction conditions. To do so, we designed a flexibly-timed procedure consisting specific actions performed by our platform when reaction-monitoring checkpoints are met. Online allowed system autonomously separate, label quantify most components, with orthogonal enabling non-UV active species be additionally tracked. tested CDI-mediated multistep amidation reactions using variety acid amine substrates. demonstrate high reproducibility afforded system, determined relative rates both activation subsequent amidation, providing insight into mechanism.