合成路线:The acylation of (-)-2,10-camphorsultam (II) with octanoyl chloride (I) provides the N-octanoyl sultam (III).Diastereoselective alkylation of the lithium enolate of (III) with allyl bromide (IV) gives rise to the (2S)-2-propenoyloctanoyl sultam (V).Hydrolysis of the N-acyl sultam (V) to furnish acid (VI) is then effected by treatment with hydrogen peroxide-tetrabutylammonium hydroxide.Finally,catalytic hydrogenation of the unsaturated acid (VI) in the presence of either Pd/C or Pt/C yields the required (R)-2-propyloctanoic acid.Alternatively,the title compound is obtained by hydrogenation of the N-acyl sultam (V) to the saturated derivative (VII),followed by hydrolytic removal of the camphorsultam moiety.
合成路线:In a related procedure,the N-octanoyl sultam (I) is alkylated by propargyl bromide (II) to produce (III).Hydrolysis of (III) by means of hydrogen peroxide-tetrabutylammonium hydroxide or lithium hydroxide-hydrogen peroxide furnishes acid (IV).Then,catalytic hydrogenation of the propargyloctanoic acid (IV) in the presence of either Pd/C or Pt/C provides the title compound.
参考文献标题:Process for the preparation of (2R)-2-propyloctanoic acid
文献作者:Iguchi,Y.; Yamaguchi,K.; Toda,N.(Ono Pharmaceutical Co.,Ltd.; Tokyo Kasei Kogyo Co.,Ltd.)
参考来源:EP 1153910; WO 0048982
合成路线:Reaction of L-prolinol (XII) with pentanoyl chloride (XIII) by means of triethylamine (TEA) in dichloromethane gives N-pentanoyl-L-prolinol (XIV),which is stereoselectively alkylated with hexyl iodide (XV) by means of butyl lithium and diethylamine (DEA) in THF to yield N-[2(R)-propyloctanoyl]-L-prolinol (XVI).This compound is subjected to purification via its esterification with 4-nitrobenzoyl chloride (XVII) and pyridine to the corresponding ester (XVIII) and recrystallization to form n-hexane.Hydrolysis of the pure ester (XVIII) with LiOH in water affords pure N-[2(R)-propyloctanoyl]-L-prolinol (XVI),which is finally treated with HCl in AcOH.
参考文献标题:Preparation method of optically active 2-propyloctanoic acid
文献作者:Nakai,H.; Kishimoto,K.(Ono Pharmaceutical Co.,Ltd.)
参考来源:JP 1996295648
合成路线:Acylation of 4(R)-benzyloxazolidin-2-one (XXXIV) with octanoyl chloride (XX) by means of t-BuOK in THF gives 3-octanoyl-4(R)-benzyloxazolidin-2-one (XXXV),which is alkylated with allyl iodide (XXXVI) and LiHMDS in THF to yield the chiral 2-allyloctanoyl amide (XXXVII).Hydrogenation of amide (XXXVII) with H2 over Pd/C in ethanol affords the corresponding 2-propyl derivative (XXXVIII),which is finally submitted to hydrolysis of the chiral auxiliary.
参考文献标题:Intermediate and process for producing optically active cpd.from the intermediate
文献作者:Tatsuta,K.(Ono Pharmaceutical Co.,Ltd.)
参考来源:WO 0351852
合成路线: Alkylation of dimethyl malonate (I) with hexyl bromide (II) by means of NaOMe in methanol gives dimethyl 2-hexylmalonate (III),which is alkylated again with 2-propynyl bromide (IV) by means of NaOMe in methanol to yield dimethyl 2-hexyl-2-(2-propynyl)malo-nate (V).Selective monodecarboxylation of malonate (V) by means of LiCl in hot DMSO affords methyl 2-(2-propyn- yl)octanoate (VI),which is hydrolyzed to the corres- ponding carboxylic acid (VII) by means of NaOH in methanol.Then,racemic acid (VII) is submitted to optical resolution by crystallization with 1(R)-phenylethylamine (VIII),followed by hydrolysis with HCl to provide 2(S)-(2-propynyl)octanoic acid (IX),which is finally hydrogenated with H2 over Pd/C in ethyl acetate.Alternatively,the racemic acid (VII) can also be obtained by alkylation of ethyl octanoate (X) with 2-pro-pynyl bromide (IV) by means of LDA in HMPA/THF to give ethyl 2-(2-propynyl)octanoate (XI) and then hydrolysis with NaOH in ethanol.
参考文献标题:Preparation method of optically active 2-propyl octanoate
文献作者:Nakai,H.; Kishimoto,K.(Ono Pharmaceutical Co.,Ltd.)
参考来源:JP 1996291106
合成路线:The acylation of (-)-2,10-camphorsultam (II) with octanoyl chloride (I) provides the N-octanoyl sultam (III).Diastereoselective alkylation of the lithium enolate of (III) with allyl bromide (IV) gives rise to the (2S)-2-propenoyloctanoyl sultam (V).Hydrolysis of the N-acyl sultam (V) to furnish acid (VI) is then effected by treatment with hydrogen peroxide-tetrabutylammonium hydroxide.Finally,catalytic hydrogenation of the unsaturated acid (VI) in the presence of either Pd/C or Pt/C yields the required (R)-2-propyloctanoic acid.Alternatively,the title compound is obtained by hydrogenation of the N-acyl sultam (V) to the saturated derivative (VII),followed by hydrolytic removal of the camphorsultam moiety.
合成路线:In a related procedure,the N-octanoyl sultam (I) is alkylated by propargyl bromide (II) to produce (III).Hydrolysis of (III) by means of hydrogen peroxide-tetrabutylammonium hydroxide or lithium hydroxide-hydrogen peroxide furnishes acid (IV).Then,catalytic hydrogenation of the propargyloctanoic acid (IV) in the presence of either Pd/C or Pt/C provides the title compound.
参考文献标题:A practical synthesis of optically active (R)-2-propyloctanoic acid: Therapeutic agent for Alzheimer's disease
文献作者:Hasegawa,T.; Yamamoto,H.
参考来源:Bull Chem Soc Jpn 2000,73(2),423
合成路线:The acylation of (-)-2,10-camphorsultam (II) with octanoyl chloride (I) provides the N-octanoyl sultam (III).Diastereoselective alkylation of the lithium enolate of (III) with allyl bromide (IV) gives rise to the (2S)-2-propenoyloctanoyl sultam (V).Hydrolysis of the N-acyl sultam (V) to furnish acid (VI) is then effected by treatment with hydrogen peroxide-tetrabutylammonium hydroxide.Finally,catalytic hydrogenation of the unsaturated acid (VI) in the presence of either Pd/C or Pt/C yields the required (R)-2-propyloctanoic acid.Alternatively,the title compound is obtained by hydrogenation of the N-acyl sultam (V) to the saturated derivative (VII),followed by hydrolytic removal of the camphorsultam moiety.
参考文献标题:A practical removal method of camphorsultam
文献作者:Hasegawa,T.; Yamamoto,H.
参考来源:Synlett 1998,(8),882
产品链接: CAS No. 185517-21-9›› 产品链接: CAS No.31080-41-8››