Use of Process Analytical Technology (Pat) in Small Molecule Drug Substance Reaction Development

From at-line to online NMR: coupling probe-based autosampler with benchtop NMR

“…These techniques are finding applications in the characterization, development, and implementation of chemical processes at all stages, from early reaction optimization on lab scale all the way to process characterization and control on manufacturing scale. 1…”

Synthesis of Rovafovir Etalafenamide (Part II): Dynamic Control for Successful Scale-Up of an Oxygen-Releasing Elimination Reaction Mediated by Oxone

“…Control of pH can be especially challenging at scale and, considering the added difficulties associated with generation of oxygen, prompted us to consider the use of a feedback loop. Although widely utilized in bioprocessing, feedback pH control has been considered inconvenient in small-molecule synthesis, and yet real-time analysis and process automation are cornerstones of process analytical technology (PAT) and Green Chemistry, and have recently received significant attention from the pharmaceutical industry. , Herein, we describe our development activities to overcome these challenges and successfully demonstrate this process at manufacturing scale. The reaction performance and its context within the synthesis of 1 are covered in the previous manuscript in this series …”