Laboratory of the future: a modular flow platform with multiple integrated PAT tools for multistep reactions. Issue 9 (17th April 2019) - Sagmeister, Peter
Abstract : The coupling of a modular microreactor platform, real-time inline analysis by IR and NMR, and online UPLC, leads to efficient optimization of a multistep organolithium transformation to a given product without the need for human intervention. Abstract : Currently, the monitoring of multistep continuous flow processes by multiple analytical sources is still seen as a resource intensive and specialized activity. In this article, the coupling of a modular microreactor platform with real-time monitoring by inline IR and NMR, in addition to online UPLC, is described. Using this platform, we rapidly generated experimental data (17 iterations in under 2 hours) to access information on the different chemical species at multiple points within the reactor and to generate process understanding. We highlight the application of the platform in the optimization of a multistep organolithium transformation. The optimized continuous flow conditions were demonstrated in a scale-out experiment with in-process monitoring to afford the desired product in 70% isolated yield and provided a throughput of 4.2 g h −1 .