In addition to cost, the environmental impact associated with the synthesis of nirmatrelvir in such an immediate and high demand situation cannot be overlooked, especially since the prescribed dosage is 3 g of total API per patient over the course of the 5-day treatment. While Pfizer's more recently reported route to nirmatrelvir 10 improves upon their originally reported methodology, 8a there are still numerous opportunities to reduce the amount of waste generated by the existing routes, especially focusing on use of a variety of organic solvents, and peptide coupling reagents. Therefore, there clearly exists an urgent need for the development of both a green and economically attractive synthesis of nirmatrelvir.