2026-04-17T18:50:07Zhttps://recercat.cat/oai/request

oai:recercat.cat:10459.1/842362025-05-04T18:28:42Zcom_2072_3622col_2072_479130

Enhanced flow synthesis of small molecules by in-line integration of sequential catalysis and benchtop twin-column continuous chromatography Sivo, Alessandra Kim, Tae Keun Ruta, Vincenzo Luisi, Renzo Osorio-Tejada, Jose Escribà i Gelonch, Marc Hessel, Volker Sponchioni, Mattia Vile, Gianvito Flow synthesis Small molecules Chromatography We report an improved approach for the integration of flow synthesis and continuous chromatography, for applications in the end-to-end preparation of pharmaceutically-relevant small molecules. It involves the combination of sequential microreactors and twin-column counter-current chromatography based on the often-used C18 columns. The column loading method ensures that the product breaking through a fully loaded first column is loaded onto the second one, avoiding waste of precious material and technological complexity associated with the use of four-to-six columns typical of simulated moving bed chromatography. The system was applied to synthesize biphenyl via Suzuki–Miyaura reaction, and was also demonstrated for other structurally-different compounds. Compared to the discontinuous and other traditional approaches, our method leads to higher isolated yields (ca. +60%), higher productivity (ca. +30%), and reduced solvent consumption (ca. −80%). A circularity and life-cycle analysis was also conducted to demonstrate the environmental benefits of the flow process. Funding from the European Commission (GV, grant agreement 101031710), Bracco Imaging (AS, VR, and GV), Fondazione Bracco (GV), and YMC Japan (TKK and MS) is gratefully acknowledged. 2022-11-16T12:58:03Z 2022-11-16T12:58:03Z 2022-09 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion https://doi.org/10.1039/D2RE00242F 2058-9883 http://hdl.handle.net/10459.1/84236 eng Reproducció del document publicat a https://doi.org/10.1039/D2RE00242F Reaction Chemistry & Engineering, 2022 cc-by-nc (c) Sivo, Alessandra et al., 2022 info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by-nc/4.0/ Royal Society of Chemistry