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    A Convenient Way To Synthesis of Analgesic Tramadol

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    Facundo Baró

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    A Convenient Way To Synthesis of Analgesic Tramadol

    Uploaded by

    Facundo Baró
    116 views1 page

    Original Title

    A Convenient Way to Synthesis of Analgesic Tramadol

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    A Convenient Way To Synthesis of Analgesic Tramadol

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    Facundo Baró

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    Abstracts of Posters

    156

    A Convenient Way to Synthesis of Analgesic Tramadol (Tramal)


    Victor A. Savelyev, Alexander G. Druganov, Elvira E. Shults, Genrikh A.Tolstikov
    Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences 9 prosp. Akad.Lavrent'eva, 630090 Novosibirsk, Russia . Fax: +7(383 2) 344752. E-mail: [email protected]

    The

    analgesic

    Tramadol

    [1-(e)-methoxyphenyl-2-(e)-dimethylaminomethylcyclohexan-1(a)-ol

    hydrochloride, trans-form] is used for the therapy of strong physical pain and has become a valuable tool in opiod research [1]. The synthetic route to Tramadol consist in interaction of 2-dimethylaminomethyl-

    cyclohexanone with organomagnesium or organolithium compounds of 3-bromoanisole in tetrahydrofurane (THF) or in THF/ether solutions [1,2]. We are investigated the possibility for use of another solvents in this reactions as well as a more convenient manner of separation of resulting products. We have observed that the ratio of isomers (Ia) and (Ib) is depended on the reaction conditions. Use a mixture 2-methyl-2-methoxypropane/THF (5:1) as solvent in Grignard reaction yield the ratio of (Ia) and (Ib) equal 72 to 28 (the ratio was detected directly from the crude reaction mixture by analytical HPLC). The better results are received in 1,4-dioxane/THF (5:1) solution, the contents of isomer (Ia) rise to 85%. The employment of 4,4-dimethyl-1,3-dioxane produced similar results. In addition, it was found that the reaction of organolithium compound of 3-bromoanisole with aminomethylcyclohexanol derivative in petrol ether leads to (Ia) and (Ib) in a ratio of 78:22. The reaction proceeds more selectively in petrol ether/THF media (ratio 86:14). The isolation of the title compound was performed by the follow. By treatment of the crude reaction mixture with 15% solution hydrogen chloride in 1,4-dioxane, hydrochlorides of (Ia) and (Ib) (95% of the title compound) are obtained in a overall yield of 55%. The following recrystallization from 1,4-dioxane leads to pure Tramadol.
    OMe

    Br

    1.

    Mg or n BuLi

    OH

    OH

    OMe

    CH2NMe2 OMe
    2. O

    +
    Ib

    H CH2NMe2

    H CH2NMe2

    Ia

    References: 1. K.Flick, E.Frankus,E.Friderichs, Arzneim.-Forsch./Drug Res., 1978, 28, 107-113. 2. Pat. Brit. 997399, 1965; Pat. USA 3652589, 1972.

    Novosibirsk Institute of Organic Chemistry. All Contents Copyright 1998

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