(422b) Palladium Removal Using Multistage Centrifugal Extractors and Process Modeling for Design Optimization

Extraction and phase separation are essential unit operations in synthetic molecule drug substance processes. There has been a lot of focus on improving synthesis and crystallization process units, however, extraction and phase separation processes are usually overlooked despite their major contributions to process cycle time and process mass intensity.

In this work, we evaluated a multistage centrifugal extractor for palladium removal after a Buckwald coupling reaction. After selecting the scavenger and establishing a baseline with batch extraction experiments, the extraction was studied in a 4-stage centrifugal extractor with varying flowrates and rotation speeds. Dynochem extraction model is used to fit the mass transfer coefficient. A first-principal model is then built to optimize flowrate and number of stages for process design.

Our calculations showed that although centrifugal extractor runs under mass-transfer-limited regime, compared to batch extraction units, centrifugal extractor can significantly improve the process throughput per unit space and improve the sustainability factors by reducing the amount of scavengers and solvents.