Issue 48, 2019

Multigram-scale flow synthesis of the chiral key intermediate of (−)-paroxetine enabled by solvent-free heterogeneous organocatalysis

Abstract

The catalytic enantioselective synthesis of the chiral key intermediate of the antidepressant (−)-paroxetine is demonstrated as a continuous flow process on multi-gram scale. The critical step is a solvent-free organocatalytic conjugate addition followed by a telescoped reductive amination–lactamization–amide/ester reduction sequence. Due to the efficient heterogeneous catalysts and the solvent-free or highly concentrated conditions applied, the flow method offers key advances in terms of productivity and sustainability compared to earlier batch approaches.

Graphical abstract: Multigram-scale flow synthesis of the chiral key intermediate of (−)-paroxetine enabled by solvent-free heterogeneous organocatalysis

Supplementary files

Article information

Article type
Edge Article
Submitted
20 set 2019
Accepted
18 out 2019
First published
18 out 2019
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY license

Chem. Sci., 2019,10, 11141-11146

Multigram-scale flow synthesis of the chiral key intermediate of (−)-paroxetine enabled by solvent-free heterogeneous organocatalysis

S. B. Ötvös, M. A. Pericàs and C. O. Kappe, Chem. Sci., 2019, 10, 11141 DOI: 10.1039/C9SC04752B

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

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