Method for preparing water-soluble polymer derivatives bearing a terminal carboxylic acid

A method for converting an orther ester of a water-soluble polymer to a water-soluble polymer bearing a terminal carboxylic acid, the method comprising the steps of:

• (i) conducting acid-catalyzed hydrolysis of the ortho ester of the water-soluble polymer to provide an intermediate ester of a water-soluble polymer;
• and
• (ii) conducting base-promoted hydrolysis on the intermediate ester of the water-soluble polymer to provide the water-soluble polymer bearing a terminal carboxylic acid,
• wherein
• the ortho ester of the water-soluble polymer has the following structure:
• the water-soluble polymer bearing a terminal carboxylic has the following structure:
• and further wherein, for each of these structures,
• POLY is a water-soluble polymer;
• (a) is either zero or one;
• X, when present, is a spacer moiety;
• (z) is an integer from 1 to 24;
• R1, in each occurrence, is independently H or an organic radical selected from the group consisting of alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, and substituted aryl;
• R2, in each occurrence, is independently H or an organic radical selected from the group consisting of alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, and substituted aryl;
• and
• each R4 is a either (i) an organic radical independently selected from the group consisting of alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, and substituted aryl, or (ii) one or more atoms that combine with another R4 or the remaining R4 moieties to form a cyclic ortho ester structure.