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DOI: 10.1055/a-1981-2727
Robust and Scalable Reductive Amination Protocol for Electron-Poor Heterocyclic Amines Using Et3SiH/TFA as Reducing Agent
Abstract
A facile reductive amination procedure for electron-poor heterocyclic amines with aromatic and aliphatic aldehydes has been developed. The key to success was the use of triethylsilane (Et3SiH) as reducing agent, in combination with trifluoroacetic acid (TFA) in refluxing CH2Cl2. The reductive aminations are fast and clean, and allow for the isolation of the alkylated amines in high yields and purity after crystallization or chromatographic purification. The robustness and scalability of the process has been demonstrated for one substrate combination on 750 g scale, leading to the isolation of the corresponding product in 93% yield.
Supporting Information
- Supporting information for this article is available online at https://doi.org/10.1055/a-1981-2727.
- Supporting Information
Publication History
Received: 08 September 2022
Accepted after revision: 17 November 2022
Accepted Manuscript online:
17 November 2022
Article published online:
12 December 2022
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For selected examples of reductive aminations with electron-deficient amines, see:
The N-acetylation is believed to be the result of nucleophilic attack by the amines on the triacetoxyborohydride and has been described in previous publications: