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Oxiracetam, CT-848, CGP-21690E, ISF-2522, Neuractiv, Oriest, Neuromet

奥拉西坦Chemical Name: 4-Hydroxy-2-oxo-1-pyrrolidineacetamide
CAS No. 62613-82-5
项目整合开发状态: Launched-1987
项目研究机构: GlaxoSmithKline (Originator)
合成路线:The reaction of ethyl iminodiacetate (I) with 2-ethoxycarbonylacetyl chloride (II) by means ot triethylamine in refluxing methylene chloride gives ethyl N-(2-ethoxycarbonylacetyl)iminodiacetate (III),which is cyclized by means of sodium ethoxide in refluxing ethanol yielding ethyl 4-hydroxy-3-(ethoxycarbonyl)-DELTA3-pyrrolin-2-one-1-acetate (IV).The isomerization of (IV) with water in refluxing acetonitrile affords ethyl pyrrolidine-2,4-dione-1-acetate (V),which is reduced with NaBH4 in dimethoxyethane to ethyl 4-hydroxypyrrolidine-2-one-1-acetate (VI).Finally,this compound is treated with ammonia in methanol.
📌 参考资料/链接:
参考文献标题:Pyrrolidine derivatives
文献作者:Pifferi,G.; Pinza,M.(ISF SpA)
参考来源:DE 2635853; FR 2320741; GB 1550160; NL 7608946; US 4118396

📄 详细内容


合成路线:The silylation of 3-hydroxy-4-aminobutyric acid (VII) with bistrimethylsilyl amine gives 3-(trimethylsilyloxy)-4-aminobutyric acid (VIII),which is cyclized to 4-(trimethylsilyloxy)-2-pyrrolidinone (IX) by heating.The treatment of (IX) with ethyl bromoacetate (A) affords ethyl 4-(trimethylsilyloxy)pyrrolidine-2-one-1-acetate (X),which by desilylation with HCl gives ethyl 4-hydroxypyrrolidine-2-one-1-acetate (VI).Finally,this compound is treated with ammonia in methanol.

参考文献标题:Preparation of pyrrolidine and pyrrolidin-2-one derivatives
文献作者:Banfi,S.; et al.(ISF SpA)
参考来源:DE 2758937; DE 2758939; ES 466856; FR 2380257; GB 1588075; JP 53101367; US 4173569


合成路线:The reaction of ethyl iminodiacetate (I) with 2-ethoxycarbonylacetyl chloride (II) by means ot triethylamine in refluxing methylene chloride gives ethyl N-(2-ethoxycarbonylacetyl)iminodiacetate (III),which is cyclized by means of sodium ethoxide in refluxing ethanol yielding ethyl 4-hydroxy-3-(ethoxycarbonyl)-DELTA3-pyrrolin-2-one-1-acetate (IV).The isomerization of (IV) with water in refluxing acetonitrile affords ethyl pyrrolidine-2,4-dione-1-acetate (V),which is reduced with NaBH4 in dimethoxyethane to ethyl 4-hydroxypyrrolidine-2-one-1-acetate (VI).Finally,this compound is treated with ammonia in methanol.

合成路线:The silylation of 3-hydroxy-4-aminobutyric acid (VII) with bistrimethylsilyl amine gives 3-(trimethylsilyloxy)-4-aminobutyric acid (VIII),which is cyclized to 4-(trimethylsilyloxy)-2-pyrrolidinone (IX) by heating.The treatment of (IX) with ethyl bromoacetate (A) affords ethyl 4-(trimethylsilyloxy)pyrrolidine-2-one-1-acetate (X),which by desilylation with HCl gives ethyl 4-hydroxypyrrolidine-2-one-1-acetate (VI).Finally,this compound is treated with ammonia in methanol.

参考文献标题:Oxiracetam
文献作者:de Angelis,L.; Blancafort,P.; Serradell,M.N.; Castar,J.
参考来源:Drugs Fut 1980,5(8),405


合成路线:The reaction of ethyl iminodiacetate (I) with 2-ethoxycarbonylacetyl chloride (II) by means ot triethylamine in refluxing methylene chloride gives ethyl N-(2-ethoxycarbonylacetyl)iminodiacetate (III),which is cyclized by means of sodium ethoxide in refluxing ethanol yielding ethyl 4-hydroxy-3-(ethoxycarbonyl)-DELTA3-pyrrolin-2-one-1-acetate (IV).The isomerization of (IV) with water in refluxing acetonitrile affords ethyl pyrrolidine-2,4-dione-1-acetate (V),which is reduced with NaBH4 in dimethoxyethane to ethyl 4-hydroxypyrrolidine-2-one-1-acetate (VI).Finally,this compound is treated with ammonia in methanol.
参考文献标题:Cyclic GABA [4-aminobutyric acid]-GABOB[4-amino-3-hydroxybutyric acid] analogs.I.Synthesis of new 4-hydroxy-2-pyrrolidinone derivatives
文献作者:Pifferi,G.; Pinza,M.
参考来源:Farmaco 1977,32(8),602-613


产品链接: CAS No. 62613-82-5››