(105b) Process Intensification Using a Continuous Packed Bed Reactor for Enzymatic Hydrolysis

Skliar, D., Bristol-Myers Squibb
Cuniere, N., Bristol-Myers Squibb
LaPorte, T. L., Bristol-Myers Squibb Company
Chuang, S., Princeton
Singh, A., Bristol-Myers Squibb
Goswami, A., Bristol-Myers Squibb

Due to their ability to afford highly selective chiral transformations under mild conditions, reactions utilizing enzymatic catalysis have been an important part of chemical and pharmaceutical manufacturing for many years.  Enzyme immobilization offers the possibility of executing enzymatic reactions in flow by using continuous packed bed reactors (PBR).  This mode of operation offers several potential advantages over standard batch operation, e.g. ability of catalyst recycle and improved throughput/cycle time due to process intensification.  In this work, process development efforts to prepare a pharmaceutical intermediate using an immobilized enzyme PBR will be presented.  It is demonstrated that a significant enhancement in reaction rate can be achieved using a PBR, allowing full conversion in τ < 5 min (vs. 24 hours in batch). Reaction kinetics and reactor performance under a variety of conditions (temperature, concentration, superficial velocity, packing density, etc.) are evaluated and analyzed.  A simple PBR kinetic model is constructed; model performance and comparison to experimental laboratory scale-up data will be discussed as well.