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.

Sterically demanding trialkylphosphines for palladium-catalyzed cross coupling reactions—alternatives to PtBu3

“…The removal of residual catalyst complex from the products of transition metal catalyzed reactions is very important for a number of reasons. [145][146][147][148] First of all there is the chance to recover valuable catalyst complexes, which often contain platinum group metals and sophisticated and thus expensive ligands. 64 Furthermore, especially for use with humans, strict limits for the contamination of chemicals with heavy metals apply, which are in the 1-10 ppm range.…”

Effective Laboratory-Scale Preparation of Axitinib by Two CuI-Catalyzed Coupling Reactions

“…[5][6][7][8][9][10] However, the high cost and residual of Pd (>25ppm after removing residual palladium by adsorption and crystallization), may not meet the demand for heavy metals content in the first-generation synthesis of axitinib, which demand for below 10ppm. 11,12 For the commercial route, a recrystallization was employed to ensure Pd levels were below 10 ppm and the formation of the desired solid form (Form XLI).…”

Synthesis of Hydrophilic Sulfur‐Containing Adsorbents for Noble Metals Having Thiocarbonyl Group Based on a Methacrylate Bearing Dithiocarbonate Moieties

“…However, thiol groups are susceptible to oxygen-converting thiols into disulfides via oxidative coupling [44]. iocarbonyl moieties such as thioamide [26][27][28][29][30][47][48][49][50][51][52][53], thiourethane [31,33,35,37], and thiourea [11,25,[54][55][56][57][58][59][60] have also been examined as stable adsorbents. We also have found that a polymer bearing N,N-dialkylthiourethane moieties has high adsorption ability to Pd and Au, but the adsorption from aqueous solutions only proceeded in the presence of organic solvents such as chloroform due to the hydrophobic nature of the backbone [35].…”