Patent ID: 6916949

Claim:
A method of synthesis comprising the steps of, in order: glutamate conjugation (GC), in which a 4-[N,N-bis(2-silyloxyethyl)aminolphenyl haloformate, activated carbonate, or activated carbamate 5, reacts with a glutamate, 15, to give an N-{4-[N,N-bis(2-silyloxyethyl)amino]phenoxycarbonyl}-L-glutamate, 6: silyloxy deprotection (SD), in which said N-{4-[N,N-bis(2-silyloxyethyl)amino]phenoxy-carbonyl}-L-glutamate, 6, is converted to an N-{4-[N,N-bis(2-hydroxyethyl)amino]phenoxycarbonyl}-L-glutamate, 7: sulfonic esterification (SE), in which said N-{4-[N,N-bis(2-hydroxyethyl)amino]phenoxycarbonyl}-L-glutamate, 7, is converted to an N-{4-[N,N-bis(2-sulfonyloxyethyl)amino]phenoxycarbonyl}-L-glutamate, 8: wherein: X 1 is a leaving group; n is an integer from 0 to 4; each R A is independently an aryl substituent; each R B is a silyl substituent, and is independently C 1-7 alkyl, C 3-20 heterocyclyl, or C 5-20 aryl, and is optionally substituted; each R C is a sulfonic substituent, and is independently C 1-7 alkyl, C 3-20 heterocyclyl, or C 5-20 aryl, and is optionally substituted; and, each Z 2 is independently a carboxylic acid protecting group.