Direct Reductive <i>N</i>‐alkylation of Amines with Carboxylic Esters

Abstract We report herein a facile direct method for the reductive N ‐alkylation of amines with carboxylic esters, using tert ‐butylmagnesium chloride ( t ‐BuMgCl) as a mediator and Red‐Al as the reducing agent. The direct amidation of esters with amines and t ‐BuMgCl generates the intermediate amides. Subsequently, without the need for isolation or purification, these intermediates reacted with Red‐Al in the same reaction flask to generate amines up to 90 % yield. This process is characterized by the rapid reaction time, quantitative conversion, and broad ester scope with various functional groups. Notably, this method enables the successful transformation of amine with carboxylic esters to produce cariprazine, a pivotal antipsychotic drug substance.

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Publication Details

Journal
European Journal of Organic Chemistry
Published
2024-11-29
DOI
https://doi.org/10.1002/ejoc.202401285
Citations
1
Primary Topic
Asymmetric Hydrogenation and Catalysis
Type
article
Field-Weighted Citation Impact
0.16

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article

Direct Reductive N‐alkylation of Amines with Carboxylic Esters

Jingshan Shen, Haji Akber Aisa, Xingbang Yang, Peng Yang et al.
1 citations
European Journal of Organic Chemistry
Asymmetric Hydrogenation and Catalysis
0.16
article

Direct Reductive N‐alkylation of Amines with Carboxylic Esters

Jingshan Shen, Haji Akber Aisa, Xingbang Yang, Peng Yang, Hongjian Qin, Emmanuel Mintah Bonku, Xiangrui Jiang, Fuqiang Zhu, Safomuddin Abduahadi, Yuxuan Zhang
article en
1 citations

Abstract

Abstract We report herein a facile direct method for the reductive N ‐alkylation of amines with carboxylic esters, using tert ‐butylmagnesium chloride ( t ‐BuMgCl) as a mediator and Red‐Al as the reducing agent. The direct amidation of esters with amines and t ‐BuMgCl generates the intermediate amides. Subsequently, without the need for isolation or purification, these intermediates reacted with Red‐Al in the same reaction flask to generate amines up to 90 % yield. This process is characterized by the rapid reaction time, quantitative conversion, and broad ester scope with various functional groups. Notably, this method enables the successful transformation of amine with carboxylic esters to produce cariprazine, a pivotal antipsychotic drug substance.

European Journal of Organic ChemistryVol. 28(1)
Shenyang Pharmaceutical University (CN), Chinese Academy of Sciences (CN), Xinjiang Technical Institute of Physics & Chemistry (CN), Shanghai Institute of Materia Medica (CN), Shanghai Zhangjiang Laboratory (CN), University of Chinese Academy of Sciences (CN), State Key Laboratory of Drug Research
West Light Foundation of the Chinese Academy of Sciences
Good health and well-being
Openalex Percentile: Top 55%
Asymmetric Hydrogenation and Catalysis
0.16
DOISourceOpenAlex
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Direct Reductive <i>N</i>‐alkylation of Amines with Carboxylic Esters — Jingshan Shen, Haji Akber Aisa, et al. · European Journal of Organic Chemistry (2024) | TGRS Research Map | TGRS