A New Direct Synthesis of Tertiary N-Acyloxymethylamide Prodrugs of Carboxylic Acid Drugs

Article abstract of DOI:10.1016/0040-4039(94)88238-X

N-Alkyl-N-chloromethylamides 2, prepared from secondary amides, paraformaldehyde and chlorotrimethylsilane, react readily with carboxylate anions to generate the corresponding tertiary N-acyloxymethylamides 3 in good yield; the latter give rise to the parent carboxylic acids in aqueous media at pH 7.4 and 37 deg C with half-lives between ca. 1 min and 42 h.