Meeting Metal Limits in Pharmaceutical Processes

Palladium-scavenging self-assembled hybrid hydrogels – reusable highly-active green catalysts for Suzuki–Miyaura cross-coupling reactions

“…Scavenging Pd from waste is therefore of key importance 12. Furthermore, Pd is considered an unacceptable contaminant in pharmaceutical products – its use in synthesis must be carefully considered, and there is a need to sequester Pd contaminants 13. There has also been intense interest in developing ‘green’ syntheses using Pd to minimise environmental costs 14.…”

Palladium Extraction Following Metal-Catalyzed Reactions: Recent Advances and Applications in the Pharmaceutical Industry

“…These have been covered in previous reviews in the literature. − The choice of palladium removal technique is very system-dependent; efficiency of removal can be affected by the reaction product, solvent, temperature, and additives . Simultaneously, metal speciation during the process may give rise to palladium species in multiple oxidation states, which require different approaches for their removal. ,, This lack of generality is unfavorable, as process development is necessary for every individual case to ensure that acceptance criteria are met without compromising product yield. The definition of acceptable palladium levels is highly dependent on the location of the metal-catalyzed step in the synthesis.…”

“…A range of purification techniques have been thoroughly investigated in attempts to achieve maximal metal removal to the process waste streams, including extraction and adsorption. These have been covered in previous reviews in the literature. − The choice of palladium removal technique is very system-dependent; efficiency of removal can be affected by the reaction product, solvent, temperature, and additives . Simultaneously, metal speciation during the process may give rise to palladium species in multiple oxidation states, which require different approaches for their removal. ,, This lack of generality is unfavorable, as process development is necessary for every individual case to ensure that acceptance criteria are met without compromising product yield.…”

“…The majority of case studies selected exemplify large-scale applications of scavenging, with some illustrative examples of the use of novel scavengers that have yet to be utilized on an industrial scale. Certain case studies that have been covered in previous reviews, however, are included herein for completeness. − Schemes in each section display the metal-catalyzed reaction, followed by the metal removal protocol, with an indication of the largest scale on which the process has been reported when values have been disclosed by the authors. Parts per million (ppm) values demonstrating the lowest palladium contents achieved using the removal protocol are also displayed when these values have been disclosed in the publication.…”

Organic photoredox catalyzed dealkylation/acylation of tertiary amines to access amides

“…However, most of these transformations rely mainly on precious metal Ru- or Ir-complexes, 3 which always suffer from the issues of high cost, potential toxicity, and pollution for terminal products. 4 Therefore, developing new organic photocatalysts with low cost, high efficiency and stability to replace these classical noble metal photocatalysts remains highly attractive and demanded. In this context, we recently have reported two new types of organic photocatalysts via rationally designed organic electric donor–acceptor (D–A) frameworks, 5 which have been successfully applied to the C(sp 3 )–H functionalization of saturated aza-heterocycles and difunctionalization of olefins.…”