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Synthesis 2002(7): 0911-0915
DOI: 10.1055/s-2002-28517
PAPER
© Georg Thieme Verlag Stuttgart · New York

1-Benzyl-4-chloromethylpiperidine: A Building Block in the Synthesis of Compounds of Pharmacological Interest

María Isabel Rodríguez-Franco*, María Isabel Fernández-Bachiller
Instituto de Química Médica (C.S.I.C.), Juan de la Cierva 3, 28006 Madrid, Spain
Fax: +34(91)5644853; e-Mail: IsabelRguez@iqm.csic.es;
Further Information

Publication History

Received 22 January 2002
Publication Date:
14 May 2002 (online)

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Abstract

The first synthesis of 1-benzyl-4-(chloromethyl)piperidine (1) is described, together with its application in the synthesis of potential pharmaceuticals. Reaction of 1 with several purines in basic medium proceed through the initial formation of 1-benzyl-1-azoniabicyclo[2.2.1]heptane system, which then undergoes nucleophilic attack at two different carbons, yielding N-benzylpiperidine and N-benzylpyrrolidine derivatives.

Key words

N-benzylpiperidines - N-benzylpyrrolidines - purines - alkylations - rearrangements

    References

  • 2 Sugimoto H. Iimura Y. Yamanishi Y. Yamatsu K. Bioorg. Med. Chem. Lett.  1992,  2:  871 
    CrossrefGoogle Scholar
  • 3 Contreras J.-M. Rival YM. Chayer S. Bourguignon J.-J. Wermuth CG. J. Med. Chem.  1999,  42:  730 
    CrossrefGoogle Scholar
  • 4 Gilligan PJ. Cain GA. Christos TE. Cook L. Drummond S. Johnson AL. Kergaye AA. McElroy JF. Rohrbach KW. Schmidt WK. Tam SW. J. Med. Chem.  1992,  35:  4344 
    CrossrefGoogle Scholar
  • 5 Boyfield I. Brown TH. Coldwell MC. Cooper DG. Hadley MS. Hagan JJ. Healy MA. Johns A. King RJ. Middlemiss DN. Nash DJ. Riley GJ. Scott EE. Smith SA. Stemp GJ. J. Med. Chem.  1996,  39:  1946 
    CrossrefGoogle Scholar
  • 6 Zhou ZL. Cai SX. Whittemore ER. Konkoy CS. Espitia SA. Tran M. Rock DM. Coughenour LL. Hawkinson JE. Boxer PA. Bigge CF. Wise LD. Weber E. Woodward RM. Keana JF. J. Med. Chem.  1999,  42:  2993 
    CrossrefGoogle Scholar
  • 7 Dutta AK. Coffey LL. Reith MEA. J. Med. Chem.  1997,  40:  35 
    CrossrefGoogle Scholar
  • 8 Dutta AK. Xu C. Reith MEA. J. Med. Chem.  1998,  41:  3293 
    CrossrefGoogle Scholar
  • 9 Ohrui H. Kohgo S. Kitano K. Sakata S. Kodama E. Yoshimura K. Matsuoka M. Shigeta S. Mitsuya H. J. Med. Chem.  2000,  43:  4516 
    CrossrefGoogle Scholar
  • 10 Hakimelahi GH. Mei N.-W. Moosavi-Movahedi AA. Davari H. Hakimelahi S. King K.-Y. Hwu JR. Wen Y.-S. J. Med. Chem.  2001,  44:  1749 
    CrossrefGoogle Scholar
  • 11 Harada H. Asano O. Hoshino Y. Yoshikawa S. Matsukura M. Kabasawa Y. Niijima J. Kotake Y. Watanabe N. Kawata T. Inoue T. Horizoe T. Yasuda N. Minami H. Nagata K. Murakami M. Nagaoka J. Kobayashi S. Tanaka I. Abe S. J. Med. Chem.  2001,  44:  170 
    CrossrefGoogle Scholar
  • 12 Rathbone MP. Middlemiss PJ. Gysbers JW. Andrew C. Herman MAR. Reed JK. Ciccaretti R. Di Iorio P. Caciagli F. Prog. Neurobiol.  1999,  59:  663 
    CrossrefGoogle Scholar
  • 13 Rodríguez-Franco MI. Dorronsoro I. Martínez A. Pérez C. Badía A. Baños JE. Arch. Pharm. (Weinheim)  2000,  333:  118 
    Google Scholar
  • 14 Martínez A. Fernandez E. Castro A. Conde S. Rodríguez-Franco MI. Baños JE. Badía A. Eur. J. Med. Chem.  2000,  35:  913 
    CrossrefGoogle Scholar
  • 15 Mitsunobu O. Synthesis  1981,  1 
    Article in Thieme ConnectGoogle Scholar
  • 16 Iwakawa M. Pinto BM. Szarek WA. Can. J. Chem.  1978,  56:  326 
    Google Scholar
  • 17 DeVita RJ. Goulet MT. Wyvratt MJ. Fisher MH. Lo J.-L. Yang YT. Cheng K. Smith RG. Bioorg. Med. Chem. Lett.  1999,  9:  2621 
    CrossrefGoogle Scholar
  • 18 Rodríguez-Franco MI. Dorronsoro I. Martínez A. Synthesis  2001,  1711 
    Article in Thieme ConnectGoogle Scholar
  • 19 DeVita RJ. Hollings DD. Goulet MT. Wyvratt MJ. Fisher MH. Lo J.-L. Yang YT. Cheng K. Smith RG. Bioorg. Med. Chem. Lett.  1999,  9:  2615 
    CrossrefGoogle Scholar
  • 20 Axelsson O. Peters D. J. Heterocycl. Chem.  1997,  34:  461 
    Google Scholar
  • 21 Ceh S. Petric A. J. Chem. Soc., Perkin Trans. 1  2000,  359 
    CrossrefGoogle Scholar
  • 22a

    Compound 2 was described in several studies, but 1H and 13C NMR data were not provided.
    Crossref
  • 22b See for example: Carroll FI. Ferguson AM. Lewis JH. J. Org. Chem.  1966,  31:  2957 
    CrossrefGoogle Scholar
  • 22c Alfaro-López J. Okayama T. Hosohata K. Davis P. Porreca F. Yamamura HI. Hruby VJ. J. Med. Chem.  1999,  42:  5359 
    CrossrefGoogle Scholar
  • 23a 1H NMR and mass spectrum of 3: Popp FD. Watts RF. J. Heterocycl. Chem.  1978,  15:  675 
    CrossrefGoogle Scholar
  • 23b 13C NMR data: Abe T. Haga T. Negi S. Morita Y. Takayanagi K. Hamamura K. Tetrahedron  2001,  57:  2701 
    CrossrefGoogle Scholar
1

This paper comprises a part of M. I. Fernández-Bachiller’s Ph.D. Thesis.