Issue 12, 2022

Enhanced flow synthesis of small molecules by in-line integration of sequential catalysis and benchtop twin-column continuous chromatography

Abstract

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.

Graphical abstract: Enhanced flow synthesis of small molecules by in-line integration of sequential catalysis and benchtop twin-column continuous chromatography

Supplementary files

Article information

Article type
Paper
Submitted
17 jun 2022
Accepted
30 aug 2022
First published
06 sep 2022
This article is Open Access
Creative Commons BY-NC license

React. Chem. Eng., 2022,7, 2650-2658

Enhanced flow synthesis of small molecules by in-line integration of sequential catalysis and benchtop twin-column continuous chromatography

A. Sivo, T. K. Kim, V. Ruta, R. Luisi, J. Osorio-Tejada, M. Escriba-Gelonch, V. Hessel, M. Sponchioni and G. Vilé, React. Chem. Eng., 2022, 7, 2650 DOI: 10.1039/D2RE00242F

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