A new postpolymerization protocol based on the reactivity of alpha,alpha-difluoroacetate esters is proposed and rationalized via a combined effort of computational and experimental methods. Reaction systems designed on the basis of computational results are characterized in detail. It is found that aminolysis of polymers featuring alpha,alpha-difluoroacetate esters results in a 100% conversion of ester units to alpha,alpha-difluoroacetamide derivatives. This indicates that the new activated ester-amine chemistry reported here offers a promising approach to postpolymerization modifications.