(267a) Development and Scale up of a Continuous Flow Reaction for API Intermediate Manufacture

Continuous processing is a growing interest in pharmaceutical industry for the development and the manufacture of active pharmaceutical ingredient (API) and upstream intermediates.  Enhanced heat and mass transfer rates inherent to continuous flow reactors are enabling chemical researchers to explore reactions that are traditionally difficult to investigate in common batch reactors.  By selecting reactors with small internal volume and operating at the appropriate flow rates, it is possible to explore reactions at short reaction times.  These features render flow reactors powerful tools for studying highly energetic reactions with unstable intermediates.  Furthermore, it may be possible to gather critical reaction data more quickly with these reactors as the continuous flow operations enable rapid, sequential experimentation. 

We present a lab-based flow reactor system used to investigate the Aldol reaction used in the production of an API intermediate.  This system was utilized to understand the impact of various reaction parameters on conversion and selectivity.  To better understand and predict the reaction performance during scale up, the reaction was studied in the lab under various mixing conditions.  The lab-scale results are in agreement with the process performance at pilot scale.