Palladium Removal from Reaction Mixtures by Fixed Bed Adsorption

The objective of this project, which was sponsored by Novartis Pharmaceuticals Corporation, was to remove palladium from a reaction mixture using a fixed bed adsorption column. Palladium is a heavy metal that is used frequently as a catalyst in many reactions in the pharmaceutical industry. Reaction mixtures can be contaminated up to 3000 ppm with palladium. A final drug substance can only contain two ppm palladium or less. For this project, the Heck coupling reaction of 4-bromobenzaldehyde and methyl acrylate was used, as it is representative of common reactions used in the pharmaceutical industry.

Adsorbents were evaluated by generating adsorption isotherms; Quadrapure TU was chosen as the adsorbent based on the high capacity of this resin at 60 ºC. The adsorption column is packed with Quadrapure TU resin and glass beads. Palladium concentration is determined using a novel HPLC method that is still in development, and verified through outside analytical lab analysis. Several adsorption column runs at various flow rates and packing geometries have been performed, with the overall goal of operating the column under conditions that promote full utilization of the resin bed. The effect of feed concentration, flow rate, and packing geometry will be discussed.