Use of a Design of Experiment (DoE) to increase process understanding of a debromination reaction
QbD methodology embraces the DoE as an essential part of product and process development. The DoE is a powerful tool that applies statistics to chemistry and allows a quick and comprehensive understanding of the studied processes. The use of DoE to optimize the different reaction parameters in manufacture of drug substance has been previously applied to optimization of the different reaction parameters, namely, reaction time, volume, temperature, equivalents of L-(S)-mandelic acid and equivalents of water in the synthesis of casopitant mesylate.
Herein is described the use of DoE to optimize and increase the process understanding of a debromination reaction via catalytic transfer hydrogenation (CTH), a key step in the synthesis of a potential drug molecule (not disclosed), using formic acid as hydrogen donor and 5% palladium on charcoal as catalyst.