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.

Direct Reductive N‐Alkylation of Amines with carboxylic Esters