• 中国精品科技期刊
  • 中国高校百佳科技期刊
  • 中国中文核心期刊
  • 中国科学引文数据库核心期刊
Advanced Search
LIU Weizhong, HE Guangwei, WANG Yinhu, HE Jianxun, WANG Kui. Synthesis of 1-(4-methylbenzyl)-2-methyl-octahydro-isoquinoline hydrochloride[J]. Journal of China Pharmaceutical University, 2016, 47(5): 548-550. DOI: 10.11665/j.issn.1000-5048.20160507
Citation: LIU Weizhong, HE Guangwei, WANG Yinhu, HE Jianxun, WANG Kui. Synthesis of 1-(4-methylbenzyl)-2-methyl-octahydro-isoquinoline hydrochloride[J]. Journal of China Pharmaceutical University, 2016, 47(5): 548-550. DOI: 10.11665/j.issn.1000-5048.20160507

Synthesis of 1-(4-methylbenzyl)-2-methyl-octahydro-isoquinoline hydrochloride

More Information
  • 1-(4-Methylbenzyl)-2-methyl-octahydro-isoquinoline hydrochloride( 1 )is the key intermediate to prepare a new type of antitussives agent phosphate dimemorfan. 4-methyl-phenylacetic acid as a raw materials, was chlorinated with thionyl chloride to obtain 4-methyl-phenylacetyl chloride, followed by reaction with 2-cyclohexenyl amine, then cyclization, reduction, methylation and salt formation by HCl were taken out to give the desired product 1 . The total yield is 54%, and the purity is greater than 98%. This synthetic process is characterized with available raw materials, simple in operation with high yield and purity, and suitable for large-scale production.
  • [1]
    Murakami M,Kawahara S,Inukai N,et al.Studies on morphinan derivatives.II.The synthesis of d-3-methyl-N-methylmorphinan,a new antitussive[J].Chem Pharm Bull,1972,20(8):1706-1710.
    [2]
    Schnider O,Hellerbach J.Synthese von morphinanen.(2.Mitteilung)[J].Helv Chim Acta,1950,33(6):1437-1448.
    [3]
    Murakami M,Inukai N,Nagano N.Studies on morphinan derivatives.I.The synthesis of several new 3-substituted derivatives of N-methylmorphinan having antitussive activities[J].Chem Pharm Bull,1972,20(8):1699-1705.
    [4]
    Gal J,Weinkam RJ,Castagnoli N.Synthesis of cis-and trans-1-(3,4-dimethoxybenzyl)-3,7-dimethyl-5,8-dimethoxy-1,2,3,4-tetrahydroxyisoquinoline.Mechanism of the Bischler-Napieralski reaction[J].J Org Chem,1974,39(3):418-421.
    [5]
    Xu YJ,Wei XY,Cong JJ,et al.Tetralin isoquinoline compounds as well as preparation methods and applications thereof(四氢异喹啉类化合物及其制备方法和用途):CN,102134245 A[P].2011-07-27.
    [6]
    Belsten JC,Dyke SF.4.Monofluoroisoquinolines.Part I[J].J Chem Soc,1964:22-26.
    [7]
    Belsten JC, Dyke SF. Monofluoroisoquinolines. Part II[J]. J Chem Soc C,1968:2073-2075.
    [8]
    Kametani T, Fukumoto K, Satoh F. The syntheses of isoquinoline alkaloids and related compounds by biogenetic type reactions[J].Bioorg Chem,1974,3(4):430-497.
    [9]
    Cope AC, Burrows WD. Clarke—Eschweiler cyclization. Scope and mechanism 1a[J].J Org Chem,1966,31(10):3099-3103.
    [10]
    Farkas E,Sunman CJ.Chiral synthesis of doxpicomine[J].J Org Chem,1985,50(7):1110-1112.
  • Related Articles

    [1]LI Zhenming, HUO Meirong, DENG Qidan, CHEN Dengjun, SUN Hongzhang. In vitro evaluation of saxagliptin and metformin hydrochloride sustained-release tablets[J]. Journal of China Pharmaceutical University, 2021, 52(5): 541-546. DOI: 10.11665/j.issn.1000-5048.20210505
    [2]ZHANG Jinlin, YUAN Yaozuo, ZHANG Ya, ZHAO Shuqiang, ZHAO Xun, ZHANG Mei. Consistency evaluation of domestic generic rifampicin capsules and reference drug in vitro[J]. Journal of China Pharmaceutical University, 2018, 49(5): 603-609. DOI: 10.11665/j.issn.1000-5048.20180513
    [3]Study on Optimize the Preparation and Formulation of Nimodipine-Containing Nanoliposome[J]. Journal of China Pharmaceutical University, 2003, (1): 27-30.
    [4]Distribution of Nimodipine Microemulsion in Mice In vivo and Evaluation on Its Targeting Performance[J]. Journal of China Pharmaceutical University, 2002, (4): 31-34.
    [5]Study on Transdermal Therapeutic System for Nimodipine[J]. Journal of China Pharmaceutical University, 2000, (5): 28-31.
    [6]Development of Nimodipine Sustained Release Capsules[J]. Journal of China Pharmaceutical University, 1999, (5): 346-349.
    [7]The Factors Influencing Nimodipine Release from Hydroxypropyl Methylcellulose Matrix Tablet[J]. Journal of China Pharmaceutical University, 1998, (6): 418-421.
    [8]Improved Process of Nimodipine[J]. Journal of China Pharmaceutical University, 1998, (3): 82-83.
    [9]Study on Penetration Enhancers for Nimodipine[J]. Journal of China Pharmaceutical University, 1994, (3): 149-152.
    [10]CORRELATION BETWEEN THE ABSORPTION IN VIVO AND THE RELEASE IN VITRO OF TWO CONTROLLED-RELEASE TABLETS OF AMINOPHYLLINE[J]. Journal of China Pharmaceutical University, 1986, (1): 18-23.

Catalog

    Article views (1067) PDF downloads (1373) Cited by()

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return