Removal of Soluble Palladium Complexes from Reaction Mixtures by Fixed-Bed Adsorption

Abstract

The increasing use of metal-containing catalysts in producing pharmaceutical intermediates and active pharmaceutical ingredients, in conjunction with requirements of low metal content in a drug substance, has motivated the development of efficient separations processes for metals removal. In this paper, fixed-bed adsorption, an attractive alternative to batch adsorption, was investigated using a reaction mixture from a Heck coupling. Adsorption isotherm determinations using three candidate adsorbents revealed that QuadraPure TU had the greatest affinity and identified the optimal adsorption temperature. The bed residence time was key in obtaining good adsorption efficiency in subsequent fixed-bed experiments. Methods for palladium detection by HPLC were developed to monitor adsorption column performance in quasi real-time. A preliminary design methodology was developed in which actual breakthrough time is estimated from the experimentally determined tradeoff between bed efficiency and residence time. Even at the realized 55% bed efficiency, fixed-bed adsorption requires less than one-fourth the adsorbent needed for a single-stage batch adsorption process.