First preliminary studies were conducted in batch mode to understand the scope for process intensification, followed by establishing feasibility of carrying out these reactions in flow reactors. The process was optimized at lab scale to identify the critical process parameters and the residence time distribution and reaction kinetics were also well-characterized. A detailed understanding of the flow process at the lab scale enabled selection of commercial equipment based on reaction requirements. As acetonide deprotection step was acidic in nature, required a high temperature and was sensitive to mixing, a silicon carbide reactor from Chemtrix® (Plantrix) was identified as the right choice. The hydrolysis was carried out in the Plantrix followed by a PFR to allow sufficient residence time and the salt exchange, which had some tendency to form precipitates, was carried out in a dynamic reactor from AM Technologies®. Next, the pilot scale feasibility and verification of design space were performed on these pilot scale equipment. Challenges faced during further scale-up to commercial equipment and their resolution will be discussed.
A control strategy comprising PAT and a diversion strategy based on residence time distribution and model-based sensitivity analysis was established for commercial operation. A greenfield facility capable of manufacturing 90 tons/annum of this API has been established.