合成路线:The reaction of 3-bromoanisole (I) with magnesium in THF gives 3-methoxyphenylmagnesium bromide (II),which is condensed with 3-bromopyridine (III) in THF by means of dichlorobis(triphenylphosphine)nickel yielding 3-(3-pyridinyl)anisole (IV).The alkylation of (IV) with propylbromide (A) in acetone at 110 C (under pressure) affords N-propyl-3-(3-methoxyphenyl)pyridinium bromide (V),which is reduced with H2 over Pt in methanol to give 1-propyl-3-(3-methoxyphenyl)piperidine (VI).Finally,this compound is demethylated by treatment with refluxing aqueous 48% HBr.The reduction of (IV) with H2 over Pt in methanol gives 3-(3-methoxyphenyl)piperidine (VII),which is acylated and reduced simultaneously with propionic acid (B) and NaBH4 in refluxing benzene to yield (VI),already obtained.
参考文献标题:3-Phenylpiperidines.Central dopamine-autoreceptor stimulating activity
文献作者:Hacksell,U.; Arvidsson,L.E.; Svensson,U.; Nilsson,J.L.G.; S醤chez,D.; Wikstrom,H.; Lindberg,P.; Hjorth,S.; Carlsson,A.
参考来源:J Med Chem 1981,24(12),1475-82
合成路线:The reaction of 3-bromoanisole (I) with magnesium in THF gives 3-methoxyphenylmagnesium bromide (II),which is condensed with 3-bromopyridine (III) in THF by means of dichlorobis(triphenylphosphine)nickel yielding 3-(3-pyridinyl)anisole (IV).The alkylation of (IV) with propylbromide (A) in acetone at 110 C (under pressure) affords N-propyl-3-(3-methoxyphenyl)pyridinium bromide (V),which is reduced with H2 over Pt in methanol to give 1-propyl-3-(3-methoxyphenyl)piperidine (VI).Finally,this compound is demethylated by treatment with refluxing aqueous 48% HBr.The reduction of (IV) with H2 over Pt in methanol gives 3-(3-methoxyphenyl)piperidine (VII),which is acylated and reduced simultaneously with propionic acid (B) and NaBH4 in refluxing benzene to yield (VI),already obtained.
参考文献标题:
文献作者:Arvidsson,F.L.E.; et al.
参考来源:EP 0030526
合成路线:The condensation of (3-methoxyphenyl)acetonitrile (VIII) with 3-bromopropyltetrahydropyranyl ether (IX) by means of lithium diisopropylamide in THF gives 2-(3-methoxyphenyl)-5-tetrahydropyranyloxypentanonitrile (X),which is oxidized with chromic anhydride-H2SO4 yielding 4-cyano-3-(3-methoxyphenyl)butyric acid (XI).The hydrolysis of (XI) with KOH in ethanol-water affords 2-(3-methoxyphenyl)glutaric acid (XII),which is anhydrized with refluxing acetic anhydride giving 2-(3-methoxyphenyl)glutaric anhydride (XIII).The reaction of (XIII) with propylamine (C) in refluxing benzene yields 2-(3-methoxyphenyl)-N-propylglutarimide (XIV),which is demethylated with BBr3 in methylene chloride to 2-(3-hydroxyphenyl)-N-propylglutarimide (XV).The benzylation of (XV) with benzyl bromide and K2CO3 in DMF affords 2-(3-benzyloxyphenyl)-N-propylglutarimide (XVI),which is reduced with LiAlH4 in THF giving 3-(3-benzyloxyphenyl)-N-propylpiperidine (XVII).Finally,this compound is debenzylated by hydrogenolysis with H2 over Pd/C in AcOH.
参考文献标题:An efficient synthesis of 3-arylpiperidines
文献作者:Brands,F.T.L.; Loozen,H.J.J.
参考来源:J R Neth Chem Soc 1981,100(9),333-336
产品链接: CAS No. 85966-89-8›› 产品链接: CAS No.75240-91-4››