This convergent route to nirmatrelvir has been accomplished in 70% overall yield, a considerable improvement over the 48% reported by Pfizer. 8a Table summarizes a direct comparison of several additional key features associated with each route with respect to environmental aspects, as well as potential costs. Importantly, given the global volumes of drug needed (leading to a projected $22 billion in revenue), and using Sheldon's E Factors 26 as a reasonable guide to waste creation, the sequence described herein is suggestive of a far more attractive process. What the E Factors do not highlight, however, is the significant decrease in hazardous waste generated, including chlorinated solvents, DMF, and excess reagents such as HATU and the Burgess reagent.