This article uses a NaOtA Bu-mediated synthetic approach was developed for the direct amidation of unactivated esters with amines under transition-metal-free and solvent-free conditions to give a range of amides in good to excellent yields at room temperature. In particular, an environmentally friendly and practical work-up procedure has been disclosed which in most cases avoids the use of organic solvents and chromatography. In addition, the production of representative products on a gram scale 3a, 3w and 3au was implemented efficiently using operationally simple, sustainable and practical procedures. In addition, this approach was also applicable to the synthesis of valuable molecules such as moclobemide (a powerful antidepressant), benodanil, and fenfuram (two commercial agricultural fungicides). These results show that this protocol can streamline amide synthesis in the industry. In the meantime, quantitative green metrics of all target products have been assessed, meaning that this protocol is advantageous over the reported ones in terms of environmental friendliness and sustainability. Finally, additional experiments and computational calculations were performed to elucidate the mechanistic insights of this transformation, and a plausible mechanism was provided based on these results and the accompanying literature reports.