Development and Scale-Up of a Direct Asymmetric Reductive Amination with Ammonia

被引：23

作者：

Brewer, Alison Campbell ^{[2
]}

Ruble, J. Craig ^{[3
]}

Vandeveer, H. George ^{[1
]}

Frank, Scott A. ^{[2
]}

Nevill, C. Richard, Jr. ^{[3
]}

机构：

[1] Albany Mol Res Inc, Albany, NY 12203 USA

[2] Eli Lilly & Co, Lilly Res Labs, Synthet Mol Design & Dev, Indianapolis, IN 46285 USA

[3] Eli Lilly & Co, Lilly Res Labs, Discovery Chem Res & Technol, Indianapolis, IN 46285 USA

来源：

ORGANIC PROCESS RESEARCH & DEVELOPMENT | 2021年 / 25卷 / 03期

关键词：

direct asymmetric reductive amination; chiral primary amine; cGMP; iPr-DUPHOS; dtbm-Segphos; ruthenium;

D O I：

10.1021/acs.oprd.0c00522

中图分类号：

O69 [应用化学];

学科分类号：

081704 ;

摘要：

Direct asymmetric reductive amination represents an efficient means of converting ketones to alpha-chiral primary amines, but reported examples are very limited. We describe the development of two sets of Ru-catalyzed conditions for the direct conversion of an aryl methyl ketone to a pharmaceutically relevant chiral primary amine. In the presence of NH3, NH4Cl, and H-2, a readily available dtbm-Segphos ruthenium catalyst can be used to prepare the desired chiral primary amine with >93% ee on multikilogram scale.

引用

页码：576 / 582

页数：7

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