(47d) Modeling Of Vapor-Liquid Equilibrium To Design A Rectifying Column For The Isolation Of An Active Pharmaceutical Ingredient Intermediate From A Biotransformation Reaction

Biocatalysis transformations are increasingly being used to circumvent complex chemical synthesis steps in the pharmaceutical industry where their ability to produce regioselective and stereoselective intermediates is exploited. This presentation reviews how modeling was used to develop a vacuum distillation concentration and solvent switch step in the purification process of a bioreduction reaction that stereoselectively reduces a ketone to an alcohol which is subsequently esterified to prepare an intermediate for an experimental Active Pharmaceutical Ingredient. Clinical material and timeline requirements dictated the need to purify two biotransformation reaction streams through an established isolation procedure where a total of 15% of the ester product was unexpectedly lost to the distillates during the final vacuum distillation step. ASPEN, a commercial process simulation program, was utilized to model the physical characteristics of the product molecule and the vapor-liquid equilibrium of the system. The simulation further predicted that the ester product could be recovered from the distillates with a high yield (>99%) using a rectifying column with an appropriate plate count and reflux rate. Ensuing experiments proved this model to be highly accurate at the laboratory, prep-lab and pilot-plant scale where ultimately 33.5 kilograms of the intermediate were isolated using a pilot scale rectifying column filled with ceramic saddle packing.