PROCESS FOR PREPARING OF THIAZOLIDINEDIONE DERIVATIVES

摘要

A novel method for preparing 5-4-[2-(5-ethyl-pyridine-2-yl)-ethoxy-benzyl thiazolidine-2,4-dione(pioglitazone HCl) is provided to provide the pioglitazone HCl with good purity by using 4-N-protected aminophenol derivative as an intermediate which does not form a lot of impurities and is easy to be purified. A method for preparing a thiazolidinedione derivative represented by the formula(1) comprises the steps of: (a) subjecting 4-N-protected aminophenol derivative represented by the formula(3)(where P is acetyl as a protection group, and L is p-toluene sulfonyloxy as a leaving group) having a leaving group(L) and a protecting group(P) and 2-(5-ethyl-pyridine-yl)-ethanol represented by the formula(4) in the presence of a base to a coupling reaction to obtain a 5-ethyl-2-[2-(4-N-protected aminophenoxy)-ethyl]-pyridine compound represented by the formula(5); and (b) hydrolyzing the compound of the formula(5) to prepare 4-[2-(5-ethyl-pyridine-2-yl)-ethoxy]-phenylamine represented by the formula(6). The method further comprises a step of subjecting the compound of the formula(6) to a Meerwein condensation and then cyclizing it with thio-urea.