Kinetics Model for Designing Grignard Reactions in Batch or Flow Operations

Abstract

This paper describes the development of a “fit for use” model for a Grignard reaction, which was used to produce an intermediate compound during the manufacture of API for edivoxetine hydrochloride. The model includes three parameters, one (kSLa) of them representing the mass-transfer component and two others (k and Ea) representing the Arrhenius dependent rate constant. Several different experiments under various conditions were conducted to fit the parameters and test the model. The model achieves several goals, namely, (1) provides an understanding of the kinetics and mass transfer, useful for designing a batch or continuous process, (2) fits and predicts the mass and energy balance for laboratory data under different conditions of reactant stoichiometry or temperatures for process safety monitoring, (3) successfully predicts process dynamics at different scales of operation, from 0.25 to 1900 L to minimize uncertainty during scale-up, (4) presents a simple way to tune the model to predict dynamics usi...