The application of chemoselective synthetic strategies, specifically protecting-group-free methods, offers substantial benefits in the development of sustainable, cost-effective, and operationally simple manufacturing processes. This aligns with one of the 12 green chemistry principles, which encourages the avoidance of unnecessary derivatization. The conventional protection-deprotection approach introduces additional non-constructive steps into the synthetic route, resulting in a lower overall yield, reduced atom economy (AE), increased waste production, and higher costs. Although numerous studies have focused on mechanochemical amide coupling, limited attention has been given to chemoselectivity in these transformations. In particular, amide bond formation in the presence of free hydroxyl groups in the starting material has not been systematically explored, and few sporadic instances of such reactions have been reported. Although the nucleophilicity of amines exceeds those of alcohols and results in the predominant acylation of the former, fast reaction rates under mechanochemical conditions enabled by high concentrations of reactants might potentially result in poor chemoselectivity. While carbodiimide-mediated peptide coupling of unmasked hydroxyamino acids was shown to occur in solution, the reported mechanochemical examples relied on the use of hydroxyl-protecting groups in serine and tyrosine. In our recent works on mechanochemical C-N bond assembly assisted by chloro-and fluoro-N,N,N',N'-tetramethylformamidinium hexafluorophosphates (TCFH and TFFH, Scheme 1), we noticed that TCFH selectively activates the carboxyl group in 4-(hydroxymethyl)benzoic acid (1) to enable its amide coupling while leaving the alcoholic group intact. On the other hand, TFFH activates the alcoholic function through the generation of highly reactive isouronium intermediates that undergo facile nucleophilic substitution with amines, a transformation in which TCFH was inefficient. This observation indicates that the protecting-group-free amide coupling of hydroxycarboxylic acids can be achieved under mechanochemical conditions, with chemoselectivity governed by the selection of a C-N coupling reagent. Based on this knowledge, we aimed to undertake a screening of the previously reported mechanochemical amide coupling protocols to identify the amidation approach with the highest tolerance to unmasked hydroxyl functionalities and outline the limits of such tolerance.