(261d) Use of In-Line FTIR for the Kinetic Study of the Reaction and Degradation of Propylene Oxide In the Synthesis of a Pharmaceutical Intermediate

The process for the manufacture of a final intermediate of an active pharmaceutical ingredient (API) is a reactive crystallization in which the product crystallizes upon formation. The conditions driving that crystallization involves reaction of R-propylene oxide with an anion of the input intermediate. During normal processing, degradation of propylene oxide competes with the desired reaction. For example, elevated water content under basic conditions promotes propylene oxide degradation, primarily to propylene glycol. In-line FTIR was used to measure the conversion of the starting material and propylene oxide along with the degradation of propylene oxide under both model and actual reaction conditions. The network of propylene oxide reactions - degradation and product formation along with mass transfer of the product (crystallization) ? was studied and modeled to increase process knowledge and to afford predictive simulation capability under various reaction conditions (temperature, stoichiometry, etc.). The process has been successfully scaled up to the pilot plant in two separate campaigns. Model results and data from both laboratory studies and pilot plant runs will be presented in this talk.