Full-Scale Continuous Mini-Reactor Setup for Heterogeneous Grignard Alkylation of a Pharmaceutical Intermediate

A reactor setup consisting of two reactors in series has been implemented for a full-scale, heterogeneous Grignard alkylation. Solutions pass from a small filter reactor into a static mixer reactor with multiple side entries, thus combining continuous stirred tank reactor (CSTR) and plug flow reactor (PFR) technologies. Through the use of the reactor train in combination with in-line NIR analysis, on scale a 35% reduction in solvent volume was realized, and the formation of a key impurity was suppressed. The mini-reactor solution achieved many of the economic advantages attributed to microreactor technology, while avoiding the difficulties associated with handling of solids in microreactors.