Method of preparing carboxylic acid functionalized polymers

A method of preparing a carboxylic-acid functionalized methoxypolyethylene glycol (m PEG), comprising:

• (i) reacting, in an organic solvent, a two-fold up to a 30-fold molar excess of a tertiary ester reagent having a structure,
• where X is a halo group, and each of R3, R4 and R5 is phenyl, with a methoxyPEG-OH (mPEG-OH) having a molecular weight selected from 10,000 Da, 15,000 Da, 20,000 Da, 25,000 Da, 30,000 Da and 40,000 Da, in the presence of base at a temperature of about 25-50° C., to thereby form a reaction mixture comprising a mPEG-tertiary ester having a structure,
• (ii) removing the organic solvent from the reaction mixture by distillation to provide a residue comprising the mPEG-tertiary ester,
• (iii) hydrolyzing the mPEG-tertiary ester by addition of a strong base in aqueous solution to the residue from (ii) to thereby form a mPEG-carboxylate salt,
• (iv) directly treating, without further isolation, the mPEG carboxylate salt from (iii) with aqueous inorganic acid to thereby provide a reaction mixture comprising a carboxylic acid-functionalized mPEG having a structure, mPEG-OCH2C(O)OH, and
• (v) isolating the carboxylic acid-functionalized mPEG from the reaction mixture, wherein the isolated carboxylic acid-functionalized mPEG contains less than 5% by weight of mPEG-OH, wherein no trifluoroacetic acid is used in the process and the methoxyPEG-OH is branched.