Trifluoroacetic Anhydride as Acylating Agent and Dehydrant in One-pot Synthesis of Nirmatrelvir

ABSTRACT

Nirmatrelvir is an effective ingredient in the anti COVID-19 drug Paxlovid. There were two key steps in the original synthetic route, which involved trifluoroacetylation and dehydration. A facile and efficient synthesis of nirmatrelvir is described in this work. Intermediate 7 was converted to nirmatrelvir in one-pot synthesis with trifluoroacetic anhydride. In addition, the condensation and deprotection conditions were optimized. The yield of nirmatrelvir produced from 1raised from 51.6% to 72.5%. © 2023,Cleveland Clinic Journal of Medicine.All Rights Reserved.