(299c) Modeling and Monitoring of a Continuous Silylation Reaction

A multidisciplinary approach was utilized to develop a mechanistic kinetic model of a continuous silylation reaction within a drug substance chemical synthesis. Analysis by mid-infrared spectroscopy and ¹H and ²⁹Si-NMR were both valuable monitoring tools toward obtaining insight into the reaction kinetics.

A multi-step kinetic mechanism was proposed based upon the experimentation and orthogonal simulation results. The impact of reaction temperature, solvent concentration, and recipe were investigated. The model has been applied to both batch and continuous processes. Discussion will include sharing key learning from the model development and its application toward risk management and understanding the feasible operating region.