To provide a manufacturing method and a purification method, which are industrially advantageous, high yielding and safe, of high-purity (S)-2-(4-methoxy-benzenesulfonylamino)-N-(methoxypolyethoxyethyl)-succinamic acid-t-butyl ester as an intermediate required for the manufacture of an inhibitor of thrombin, a blood coagulation protease.
(S)-2-(4-methoxy-benzenesulfonylamino)-succinic acid-1-t-butyl ester is caused to react with a specific chloroformate ester in the presence of an organic solvent and a base to form a mixed acid anhydride, which is then caused to react with a specific polyethylene glycol-aminoethyl-methyl ether to give (S)-2-(4-methoxy-benzenesulfonylamino)-N-(methoxypolyethoxyethyl)-succinamic acid-t-butyl ester represented by formula (1) (wherein n is an integer of 20-200) without using expensive HBTU.
NOJIMA AKIKO