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. 2021 Oct 15;86(20):14232-14237.
doi: 10.1021/acs.joc.1c02350. Epub 2021 Oct 1.

Mechanochemical Synthesis of Primary Amides

Jorge Gómez-Carpintero  1 , J Domingo Sánchez  1 , J Francisco González  1 , J Carlos Menéndez  1
Affiliations

Mechanochemical Synthesis of Primary Amides

Jorge Gómez-Carpintero et al. J Org Chem. .

Abstract

Ball milling of aromatic, heteroaromatic, vinylic, and aliphatic esters with ethanol and calcium nitride afforded the corresponding primary amides in a transformation that was compatible with a variety of functional groups and maintained the integrity of a stereocenter α to carbonyl. This methodology was applied to α-amino esters and N-BOC dipeptide esters and also to the synthesis of rufinamide, an antiepileptic drug.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1
Figure 1
Representative drugs containing a primary amide group.
Scheme 2
Scheme 2. Scope of the Mechanochemical Primary Amide Synthesis
Scheme 3
Scheme 3. Synthesis of the Antiepileptic Drug Rufinamide Using Mechanochemical Conditions for the Primary Amide Formation Step
See this image and copyright information in PMC

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