5. Application of Scavengers for the Removal of Palladium in Small Lot Manufacturing

Scavengers are useful for the removal of palladium from organic products originating from palladium catalyzed reactions. Their ease of use and reliable performance with low risk for byproduct formation make them excellent candidates for early-phase process development efforts. A workflow for development of Pd scavenging process is described from screening to implementation. A small volume (1 mL) screening protocol is described and compared to a literature method. Screening experiments employ analysis by ICP/MS and HPLC to identify hits for further evaluation and process development. Some scavengers, including certain polypropylene bound scavengers and trimercaptotriazine, have a marked influence of temperature on Pd removal efficiency, making room temperature screening unreliable. Other scavengers, including some silica bound scavengers were less dependent on temperature under the screening protocol. Process development studies define the reaction progress of removing Pd, the influence of scavenger loading and the loss of product to adsorption. Demonstration of Pd scavenging on multi-kilogram production scale is described.