A Practical Transferring Method from Batch to Flow Synthesis of Dipeptides via Acid Chloride Assisted by Simulation of the Reaction Rate

This paper proposes a technical approach for seamlessly setting the conditions of continuous flow synthesis from batch data. We directly detected the acid chloride formation from Fmoc-L-Phe-OH in batch using the in-line monitoring technology ReactIR and logically calculated the residence time under continuous flow conditions based on kinetic study. Assisted by this simulation method, the sequential flow operations, which consist of acid chloride formation from Fmoc-L-Phe-OH, cooling and coupling with Fmoc-L-Phe-Cl and H2N-L-Phe-OMe, were completed in approximately 1 min.

Automated summary

This paper proposes a technical approach to determine the conditions of continuous flow synthesis from batch data, by directly detecting acid chloride formation and calculating residence time. With the assistance of simulation method, sequential flow operations can be completed in approximately 1 minute.