title: Amide-Assisted Hydrolysis of beta-Carboxamido-Substituted Phosphinic Acid Esters.
abstract: Phosphinic acids are of interest due to their ability to inhibit metalloproteases. The hydrolysis of a phosphinic acid ester is typically one of the final steps in the synthesis of such inhibitors. We have found that the acid-catalyzed hydrolysis of a phosphinic acid ester containing a beta-carboxamido group is facilitated by the presence of the amide. The promotion of the hydrolysis is dependent on the electron density of the amide suggesting the intermediacy of a cyclic imidate structure (C). The hydrolysis of phosphinic acid esters containing a beta-carboxamido group is conveniently and quantitatively effected by treating the ester with 10:90 H(2)O:TFA.
authors.affiliation: Department of Medicinal Chemistry, Central Research Division, Pfizer Inc., Groton, Connecticut 06340.
authors.forename: Lawrence A.
authors.initials: LA
authors.lastname: Reiter
authors.forename: Brian P.
authors.initials: BP
authors.lastname: Jones