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

被引：47

作者：

Oetvoes, Sandor B. ^{[1
]}

Pericas, Miquel A. ^{[2
,3
]}

Kappe, C. Oliver ^{[1
,4
]}

机构：

[1] Karl Franzens Univ Graz, NAWI Graz, Inst Chem, Heinrichstr 28, A-8010 Graz, Austria

[2] BIST, Inst Chem Res Catalonia ICIQ, Av Paisos Catalans 16, E-43007 Tarragona, Spain

[3] Univ Barcelona, Dept Quim Inorgan & Organ, E-08028 Barcelona, Spain

[4] RCPE, Ctr Continuous Synth & Proc CCELOW, Inffeldgasse 13, A-8010 Graz, Austria

来源：

CHEMICAL SCIENCE | 2019年 / 10卷 / 48期

基金：

奥地利科学基金会;

关键词：

ACTIVE PHARMACEUTICAL INGREDIENTS; DIARYLPROLINOL SILYL ETHERS; ALPHA; BETA-UNSATURATED ALDEHYDES; ENANTIOSELECTIVE SYNTHESIS; MICHAEL ADDITION; FORMAL SYNTHESIS; CATALYSTS; DERIVATIVES; AMINATION; CHEMISTRY;

D O I：

10.1039/c9sc04752b

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

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.

引用

页码：11141 / 11146

页数：6

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