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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.

SUBMITTER: Otvos SB

PROVIDER: S-EPMC7069365 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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

Ötvös Sándor B SB Pericàs Miquel A MA Kappe C Oliver CO

Chemical science 20191018 48

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 produc ...[more]

PMID: 32206263

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