In continuing our group efforts to develop scalable routes to APIs under cost effective and environmentally friendly conditions, and in an ongoing partnership with the Bill and Melinda Gates Foundation initially formed for purposes of preparing APIs for the treatment of malaria (e.g., pyronaridine), 11a we have developed a route to nirmatrelvir that simultaneously addresses these issues while maximizing both time and pot economies (Scheme 1). Furthermore, special attention has been directed towards avoiding epimerization of chiral centers during crucial peptide bond-forming steps. Workups, which often give rise to enormous volumes of both organic and aqueous waste, have also been streamlined; only simple, in-pot aqueous washes are involved, as are minimal amounts of far greener (and recoverable) organic solvents (e.g., EtOAc). The strategy selected for the synthesis of nirmatrelvir, therefore, focused on the inherent benefits on scale of a convergent route. Moreover, it seemed advantageous to perform our Pd-catalyzed amide dehydration 15 in this convergent fashion, as subsequent steps provide opportunities to limit the amount of residual Pd in the final API.