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Direct Asymmetric Reductive Amination for the Synthesis of (S)-Rivastigmine.

ABSTRACT: In this article we demonstrate how asymmetric total synthesis of (S)-rivastigmine has been achieved using direct asymmetric reductive amination as the key transformation in four steps. The route started with readily available and cheap m-hydroxyacetophenone, through esterification, asymmetric reductive amination, N-diphenylmethyl deprotection and reductive amination, to provide the final (S)-rivastigmine in 82% overall yield and 96% enantioselectivity. In the asymmetric reductive amination, catalysed by the iridium?phosphoramidite ligand complex and helped by some additives, the readily prepared 3-acetylphenyl ethyl(methyl)carbamate directly reductively coupled with diphenylmethanamine to yield the chiral amine product in 96% ee and 93% yield.

SUBMITTER: Gao G

PROVIDER: S-EPMC6225309 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Direct Asymmetric Reductive Amination for the Synthesis of (S)-Rivastigmine.

Gao Guorui G Du Shaozhi S Yang Yang Y Lei Xue X Huang Haizhou H Chang Mingxin M

Molecules (Basel, Switzerland) 20180831 9

In this article we demonstrate how asymmetric total synthesis of (S)-rivastigmine has been achieved using direct asymmetric reductive amination as the key transformation in four steps. The route started with readily available and cheap m-hydroxyacetophenone, through esterification, asymmetric reductive amination, N-diphenylmethyl deprotection and reductive amination, to provide the final (S)-rivastigmine in 82% overall yield and 96% enantioselectivity. In the asymmetr ...[more]

PMID: 30200331

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