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    • 59. 发明公开
    • 2-[(2,6-디클로로페닐)아미노]페닐아세톡시아세트산의제조방법
    • 2 - ((2,6-二氯苯基)氨基)苯甲酰氧基酸的制备方法
    • KR1020000010402A
    • 2000-02-15
    • KR1019980031302
    • 1998-07-31
    • 하나제약 주식회사
    • 장사정이점증유준식
    • C07C227/00C07C229/00
    • Y02P20/55
    • PURPOSE: A process for manufacturing 2-((2,6-dichlorophenyl)amino)phenyl acetoxy acetic acid by using an organic amine addition salt of carboxylic acid is provided which has a high yield of reactivity and easiness of removing a protecting group. CONSTITUTION: 2-£(2,6-Dichlorophenyl)amino|phenyl acetic acid is reacted with stoichiometric organic amine in the presence of organic solvent to give 2-£(2,6-dichlorophenyl)amino|phenyl acetic acid. trialkylamine salt, which is reacted with phenacyl 2-haloacetate to give 2-£(2,6-dichlorophenyl)amino|phenyl acetate, which is forced to remove a R1 protecting group to give 2-£(2,6-dichlorophenyl)amino|phenyl acetoxy acetic acid(I). For an example, 2.96g 2-£(2,6-dichlorophenyl)amino|phenyl acetic acid is dissolved in 30 ml ethyl acetate, added slowly with 1.01g triethylamine at 20-30°C.C.C, agitated for 30 min, and mixed with 2.72g 2-methanesulfonylacetate phenacyl ester for 48 hr. The reactant is filtrated to remove an insoluble salt, washed with 1N hydrochloric acid, saturated sodium dicarbonate and water, and recrystallized with methylenechloride-hexane to give 4.63g 2-£(2,6-dichlorophenyl)amino|phenyl acetoxyacetate phenacyl ester, which(1g) is dissolved in 10 ml acetic acid. added with 0.344g zinc and 30ml methylene chloride to give 0.69g 2-((2,6-dichlorophenyl)amino)phenyl acetoxy acetic acid(93%).
    • 目的:提供通过使用羧酸的有机胺加成盐制备2 - ((2,6-二氯苯基)氨基)苯基乙酰氧基乙酸的方法,其具有高的反应性产率和除去保护基的容易性。 构成:在有机溶剂存在下,将2-(2,6-二氯苯基)氨基|苯基乙酸与化学计量的有机胺反应,得到2-(2,6-二氯苯基)氨基苯基乙酸。 其与2-卤代乙酸苯甲酰酯反应,得到2-(2,6-二氯苯基)氨基|苯基乙酸酯,其被迫去除R 1保护基团,得到2-(2,6-二氯苯基)氨基 |苯基乙酰氧基乙酸(I)。 例如,将2.96g 2-(2,6-二氯苯基)氨基|苯基乙酸溶于30ml乙酸乙酯中,在20-30℃下缓慢加入1.01g三乙胺,搅拌30分钟,并与 2.72g 2-甲磺酰基乙酸酯苯甲酰甲酯48小时。 将反应物过滤除去不溶性盐,用1N盐酸,饱和二碳酸钠和水洗涤,用二氯甲烷 - 己烷重结晶,得到4.63g 2-(2,6-二氯苯基)氨基|苯基乙酰氧基乙酸酯苯甲酰甲酯,其中 (1g)溶于10ml乙酸中。 加入0.344g锌和30ml二氯甲烷,得到0.69g 2 - ((2,6-二氯苯基)氨基)苯基乙酰氧基乙酸(93%)。