PROCESS FOR ENVIRONMENT-FRIENDLY MANUFACTURING GLIMEPIRIDE BY USING NO PHENYLETHYLISOCYANATE AND TRANS-4-METHYL-CYCLOHEXYLISOCYANATE WHICH ARE EXPENSIVE AND PREPARED BY USING DEADLY POISON GAS WITH HIGH PURITY AND YIELD

摘要

PURPOSE: A process for manufacturing glimepiride is provided, which glimepiride is environment-friendly manufactured by using no phenylethylisocyanate and trans-4-methyl-cyclohexylisocyanate which are expensive and prepared by using deadly poison gas with high purity and yield. CONSTITUTION: The process for manufacturing glimepiride of reaction formula (2) comprises the steps of: (a) reacting hydroxycarbamoyl chloride(HCC) with sodiumazide to prepare hydroxycarbamoylazide, and reacting it with 3-ethyl-4-methyl-2-oxo-3-pyroline at 40 to 120 deg. C to prepare 3-ethyl-4-methyl-2-oxo-3-pyroline-1-(N-2-phenylethyl)-carboxamide of formula (3); (b) reacting 3-ethyl-4-methyl-2-oxo-3-pyroline-1-(N-2-phenylethyl)-carboxamide with chlorosulfonate to prepare 4-£2-(3-ethyl-4-methyl-2-oxo-3-pyroline-1-carboxamido)-ethyl|-benzenesulfonylchloride, and reacting it with ammonia to prepare 4-£2-(3-ethyl-4-methyl-2-oxo-3-pyroline-1-carboxamido)-ethyl|-benzenesulfonamide of formula (4); and (c) reacting 4-£2-(3-ethyl-4-methyl-2-oxo-3-pyroline-1-carboxamido)-ethyl|-benzenesulfonamide of formula (4) with an activated intermediate prepared by reacting N,N-carbonyldiimidazol(CDI) with trans-4-methyl-cyclohexylamine of formula (6), in the presence of base, wherein the base is organic base, alkali earth metal inorganic base or alkali metal inorganic base.