Once the individual steps associated had been assessed using the same T3P-mediated peptide bond formation, a 3-step, 1-pot sequence was investigated anticipated to arrive at Nirmatrelvir as its MTBE solvate 6 (Scheme 4). Carboxylic acid 1 was activated by T3P in the presence of DIPEA at -10 o C for a period of one hour. Bicyclic proline Na salt 2 was then added portion-wise at 0 o C, followed by dilution with anhydrous EtOAc. The resulting mixture was then warmed slowly to rt with stirring for 20 hours. After this period of time, the mixture was diluted with a minimal amount of EtOAc, at which point aqueous acid was added to the reaction vessel to remove by-products generated from T3P. Removal of the aqueous medium from the flask followed by concentration under vacuum to remove EtOAc afforded carboxylic acid 3. After azeotropic drying with anhydrous toluene to remove traces of residual water, the newly formed carboxylic acid 3 was then treated with aminonitrile hydrochloride 4/ DIPEA followed by dropwise addition of a 50 w/w % T3P solution in EtOAc at -10 o C. The mixture was then stirred at -10 o C for five minutes and then slowly warmed to ambient temperature at which time stirring was continued for three hours. The reaction mixture was then diluted with EtOAc and subjected to an aqueous wash using 1 M HCl. Solvent removal afforded crude 5 which was then exposed to 1:10 EtOAc: MTBE giving Nirmatrelvir as its MTBE solvate 6 in an overall isolated yield of 53%.