(126d) Application of a Dynamic Flow Reactor Platform for Data-Rich Experimentation of Complex Flow Reactions

Advancements in continuous processing technologies in parallel with the expansion of complex organic reactions enabled by flow chemistry have led to the increasing use of flow reactions throughout the pharmaceutical industry. However, to date, reaction development in flow is plagued by the inefficiencies associated with collecting data under steady-state conditions and data-rich experimentation options for characterizing flow reactions remain sparse. In the early stages of drug development, this challenge is compounded by limited availability of key raw materials and short development timelines. Transient reaction experiments provide a viable process development intensification option to lessen the resource burden and inefficiencies surrounding flow reaction process development; this approach has recently been successfully implemented to rapidly obtain kinetic profiling data [1-4].

This work focuses on the application of a recently developed automated continuous flow reactor, capable of well-defined transient experiments, to study two reaction cases where performing the chemical transformation in a flow reactor offers several benefits over a comparable batch operation: mixing sensitive and photochemical reactions. As these complex reaction systems are sensitive to reactor geometry and configuration, operating these flow reactions dynamically allows for the efficient screening of numerous reaction conditions in the specific reactor of interest. Furthermore, this added experimental efficiency can enable more facile testing of various reactor configurations (i.e., different static mixers, light sources). For example, using controlled transient flowrates and various pressure sensors, numerous mixing intensities can be screened in a single experiment and translated into trends relating reaction performance to mixing time. Similarly, any controlled transient variations in residence time, photocatalyst equivalents, and reaction concentration at various light intensities can potentially elucidate the relationship between photon equivalents, catalyst equivalents, and reaction concentration. Scale-up of these dynamic/transient flow test cases to kilo scale flow reactors may also be discussed.

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