In the pharmaceutical industry, liquid-liquid extractions are generally carried out in a batch process and used for purification purposes. However, during commercial route development for a HCV NS5B protein inhibitor, a condensation reaction became problematic due to equilibrium limited conversion. The focus of the presentation will be a strategy for implementing a scalable continuous extraction to drive an equilibrium-limited reaction to completion. The approach developed is both simple (requires common equipment and glassware found in most labs) and can be modified to meet process needs such as reduced cycle time or reduced waste solvent. Through the use of continuous extraction, we were able to push an equilibrium-limited reaction that typically stalled at 50% conversion to full conversion and improve overall process robustness. The investigation of process parameters, such as flow rate of the extracting solvent into the system, will be discussed. In addition, the results of a laboratory scale-up experiment will be presented.

Scale-up of a continuous extraction process for driving an equilibrium-limited reaction to completion

2019 Fall National Meeting

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