Highly Functionalised Sulfur-Based Silica Scavengers for the Efficient Removal of Palladium Species from Active Pharmaceutical Ingredients

Abstract

The use of multidentate sulfur-based silica scavengers 1, 2, and 3 as highly effective adsorbents for the removal of precious metals, specifically palladium residues in this paper, from highly functionalised synthetic intermediates and APIs is described. The synthesis and purification of the polar and electron-rich reaction products, containing multiple functional groups, from palladium-catalysed removals of commonly used protecting groups such as benzyl, benzyloxycarbonyl, and allyloxycarbonyl and Sonogashira, Suzuki, Heck, and Buchwald-Hartwig coupling reactions is reported. The significant levels of residual palladium species, typically associated with these reaction products, are successfully and rapidly removed to below acceptable regulatory levels, of less than 5 ppm, by simple, unoptimised treatment with the designed silica scavengers at room temperature. Performance aspects, including broad solvent compatibility, excellent stability, and high metal affinity, combined with large-scale availability, ease of handling, and minimal loss of API make these silica scavengers particularly useful to process development groups.

Strong evidence of solution-phase catalysis associated with palladium leaching from immobilized thiols during Heck and Suzuki coupling of aryl iodides, bromides, and chlorides

“…Mercaptopropyl-modified surfaces, such as SH-SBA-15, have been used as effective palladium scavengers [36,[53][54][55] as well as scavengers for other metals, such as silver and mercury [56]. SH-SBA-15 is a rigid mesoporous solid that does not swell under reaction conditions, a previously mentioned drawback of ligands immobilized on polymers such as PVPy.…”

Why is RCM Favoured Over Dimerisation? Predicting and Estimating Thermodynamic Effective Molarities by Solution Experiments and Electronic Structure Calculations

“…Where solvent-suppression techniques were employed, samples were analysed at using a Bruker AVANCE II + 600 MHz NMR spectrometer (with triple-resonance TBI-z probe) (128 scans, D 1 = 2 s). Reaction mixtures for GC-MS or detailed NMR spectroscopy analyses were stirred over PhosphonicS STA3 silica-supported metal scavenger overnight [35] and checked by 1 H NMR spectroscopy before further analyses. More detailed experimental information can be found in the Supporting Information.…”

Purified polar polyfluorene for light-emitting diodes and light-emitting electrochemical cells

“…The functional groups such as hydroxyl, amino, carboxylic acids, nitriles or aminoacids groups can form a very strong affinity for the residual Pd metal to remove it from the products. It has been reported to be effective to remove Pd catalyst in polar reaction product [22] . The ICP tests show that the Pd catalyst in EO-PF1 is 149 × 10 −6 .…”

“…ICP testing results of EO-PF1 and EO-PF2 show that after purification Pd catalyst can be removed. Although the Pd catalyst scavenging conditions described in this paper are unoptimised and scavenging efficiency is affected by a number of experimental factors, including contact time, temperature and concentration, as well as the nature of the structural groups present within the functionalised silica scavenger [22] , our purification method is very efficiency for Pd catalyst scavenging. The number-average and weight-average molecular weight of EO-PF1 and EO-PF2 determined by GPC using a polystyrene standard is M n = 24000, M w = 122000 and M n = 28000 and M w = 225000, respectively.…”