- Highly functionalised sulfur-based silica scavengers for the efficient removal of palladium species from active pharmaceutical ingredients
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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.
- Galaffu, Nicola,Man, Siud Pui,Wilkes, Robin D.,Wilson, John R. H.
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p. 406 - 413
(2012/12/31)
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- Solid-phase synthesis of 4-aminopiperidine analogues using the Alloc protecting group: An investigation of Alloc removal from secondary amines
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A useful method for Alloc removal from secondary amines on solid-phase has been optimised. The use of Me2NH·BH3 (40 equiv., 40 min) as scavenger of the allyl cations in a palladium-catalysed process with Pd[PPh3]4 leads to quantitative removal of the Alloc group without any allyl back alkylation. Other scavengers such as morpholine or PhSiH3 are clearly inferior. Furthermore, this study has highlighted differences in the reaction kinetics of the deprotection step between secondary and primary amines such as those from α-amino acids.
- Fernández-Forner, Dolors,Casals, Gaspar,Navarro, Eloísa,Ryder, Hamish,Albericio, Fernando
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p. 4471 - 4474
(2007/10/03)
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