Direct Amidation of Esters via Ball Milling

10 May 2021, Version 1
This content is a preprint and has not undergone peer review at the time of posting.

Abstract

The direct mechanochemical amidation of esters – enabled by ball-milling – is herein described. The operationally simple procedure requires inputs of ester, amine, and sub-stoichiometric KOtBu and is applicable to a preparation of a large and diverse library of 78 amide structures with modest to excellent efficiency. Heteroaromatic and heterocyclic components are specifically shown to be amenable to this mechanochemical protocol. This direct synthesis platform has been applied to the synthesis of API’s, agrochemicals, and its ability to deliver gram-scale synthesis of active pharmaceuticals and building blocks is demonstrated, all in the absence of a reaction solvent.

Keywords

mechanochemistry
ball milling
amides
amidation

Supplementary materials

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Direct Amidation Supporting Information
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