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Ifoxetine sulfate(Rec INNM), CGP-15210G

伊福西汀Chemical Name: (?-Bis[cis-3-hydroxy-4-(2,3-dimethylphenoxy)piperidine] sulfate
CAS No. 66208-11-5 (free base)
项目整合开发状态: Phase II
项目研究机构: Novartis (Originator)
合成路线:Reaction of the N-carbobenzyloxy-protected tetrahydropyridine derivative (I) with m-chloroperbenzoic acid (MCPBA) in ethylene chloride gives the stable oily epoxide (II),which,upon treatment with 2,3-dimethyphenol in acetonitrile in the presence of aqueous NaOH,affords the crystalline trans-3 hydroxy-4-phenoxy derivative (III).Oxidation of this aicohol to the corresponding ketone (IV) is best achieved by means of DMSO reagents,in particular DMSO and pyridine-SO3 adduct.Treatment of the ketone (IV) with potassium tri-sec-butylborohydride (K-Selectride(R)) in THF yields the cis-3-hydroxy-4-phenoxy derivative (V) in a highly stereoselective reaction.Hydrogenation of (V) with H2 over Pd/C in ethanol and subsequent salt formation with aqueous H2SO4 leads to racemic,diastereomerically pure CGP-l5210 G.
📌 参考资料/链接:
参考文献标题:Derivs.of perhydro-aza-heterocycles
文献作者:Paioni,R.(Novartis AG)
参考来源:DE 2738477; US 4160837

📄 详细内容


合成路线:Reaction of the N-carbobenzyloxy-protected tetrahydropyridine derivative (I) with m-chloroperbenzoic acid (MCPBA) in ethylene chloride gives the stable oily epoxide (II),which,upon treatment with 2,3-dimethyphenol in acetonitrile in the presence of aqueous NaOH,affords the crystalline trans-3 hydroxy-4-phenoxy derivative (III).Oxidation of this aicohol to the corresponding ketone (IV) is best achieved by means of DMSO reagents,in particular DMSO and pyridine-SO3 adduct.Treatment of the ketone (IV) with potassium tri-sec-butylborohydride (K-Selectride(R)) in THF yields the cis-3-hydroxy-4-phenoxy derivative (V) in a highly stereoselective reaction.Hydrogenation of (V) with H2 over Pd/C in ethanol and subsequent salt formation with aqueous H2SO4 leads to racemic,diastereomerically pure CGP-l5210 G.

参考文献标题:Ifoxetine sulfate
文献作者:Waldmeier,P.C.; Paioni,R.; Delini-Stula,A.
参考来源:Drugs Fut 1987,12(2),126


合成路线:Reaction of the N-carbobenzyloxy-protected tetrahydropyridine derivative (I) with m-chloroperbenzoic acid (MCPBA) in ethylene chloride gives the stable oily epoxide (II),which,upon treatment with 2,3-dimethyphenol in acetonitrile in the presence of aqueous NaOH,affords the crystalline trans-3 hydroxy-4-phenoxy derivative (III).Oxidation of this aicohol to the corresponding ketone (IV) is best achieved by means of DMSO reagents,in particular DMSO and pyridine-SO3 adduct.Treatment of the ketone (IV) with potassium tri-sec-butylborohydride (K-Selectride(R)) in THF yields the cis-3-hydroxy-4-phenoxy derivative (V) in a highly stereoselective reaction.Hydrogenation of (V) with H2 over Pd/C in ethanol and subsequent salt formation with aqueous H2SO4 leads to racemic,diastereomerically pure CGP-l5210 G.
参考文献标题:CGP 15 210 G,an unusual inhibitor of serotonin (5-HT) uptake
文献作者:Paioni,R.; et al.
参考来源:VIIIth Intl Symp Med Chem (Aug 27-31,Uppsala) 1985,2130


产品链接: CAS No. 66208-11-5››