The aminonitrile hydrochloride salt 4 used in the second peptide coupling (Scheme 5) was prepared from commercially available methyl ester 7 via initial hydrolysis and conversion to the known primary amide 8. Dehydration of the primary amide to afford the corresponding nitrile was accomplished by treatment with trifluoroacetic anhydride (TFAA) and N-methylmorpholine (NMM) in 2-MeTHF, as reported by Shanahan et al. The N-Boc-protected aminonitrile was then subjected to Boc-deprotection using 4 M HCl/dioxane in anhydrous acetonitrile at 0 to 10 o C over two hours, as described in our previous route to Nirmatrelvir. The bicyclic proline Na salt 2 used in the first peptide coupling was prepared following the reported protocol by Pfizer. 4