Patent ID: 8067505

Claim:
A method comprising i) reacting, in an organic solvent, a molar excess of an ester reagent of the following structure wherein: X is a leaving group; each of R 1 and R 2 is independently selected from hydrogen, alkyl, cycloalkyl, alkoxy, aryl, aralkyl, and heterocycle; each of R 3 -R 5 is independently selected from lower alkyl, aryl, aralkyl, and cycloalkyl, where any of R 3 -R 5 may be linked to form a ring or ring system; where any of R 1 to R 5 , excepting hydrogen, may be substituted with a group selected from lower alkyl, lower alkoxy, C3-C6 cycloalkyl, halo, cyano, oxo (keto), nitro, and phenyl; and n is 1 to about 24, with a 4-arm PEG-OH to form a 4-arm PEG-tertiary ester, ii) removing the organic solvent; iii) combining the 4-arm PEG-tertiary ester with water; iv) treating the 4-arm PEG-tertiary ester with a strong base in aqueous solution, to form a 4-arm PEG-carboxylate salt; and v) treating the 4-arm PEG-carboxylate salt with an inorganic acid in aqueous solution, to convert the carboxylate salt to a carboxylic acid, thereby forming a 4-arm PEG-carboxylic acid.