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Synthesis 2008(12): 1841-1844  
DOI: 10.1055/s-2008-1067084
PAPER
© Georg Thieme Verlag Stuttgart · New York

Selective Nosylation of 1-Phenylpropane-1,3-diol and Perchloric Acid Mediated Friedel-Crafts Alkylation: Key Steps for the New and Straightforward Synthesis of Tolterodine

Kathlia A. De Castro, Hakjune Rhee*
Department of Chemistry and Applied Chemistry, Hanyang University, Ansan Sa-3-Dong 1271, Kyunggi-Do 426-791, Korea
Fax: +82(31)4073863; e-Mail: hrhee@hanyang.ac.kr;
Further Information

Publication History

Received 6 February 2008
Publication Date:
16 May 2008 (online)

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Abstract

We have developed a new and straightforward synthesis of racemic tolterodine [N,N-diisopropyl-3-(2-hydroxy-5-methyl­phenyl)-3-phenylpropanamine]. The synthesis involves selective nosylation on the primary alcohol of 1-phenylpropane-1,3-diol using 4-nitrobenzenesulfonyl chloride, subsequent diisopropylamine substitution, and Friedel-Crafts alkylation using aqueous perchloric acid.

Key words

drugs - diol - selective sulfonation - nucleophilic substitution - Friedel-Crafts alkylation

    References

  • 1a Nilvebrant L. Life Sci.  2001,  68:  2549 
    CrossrefGoogle Scholar
  • 1b Chancellor MB. Appell RA. Sathyan G. Gupta SK. Clin. Therapeut.  2001,  23:  753 
    CrossrefGoogle Scholar
  • 1c Kaur K. Aeron S. Bruhaspathy M. Shetty SJ. Gupta S. Hegde LH. Silamkoti ADV. Mehta A. Chugh A. Gupta JB. Sarma PKS. Kumar N. Bioorg. Med. Chem. Lett.  2005,  15:  2093 
    CrossrefGoogle Scholar
  • 2a Gage JR, and Cabaj JE. inventors; WO  199829402. 
    Crossref
  • 2b Botteghi C. Corrias T. Marchetti M. Paganelli S. Piccolo O. Org. Process Res. Dev.  2002,  6:  379 
    CrossrefGoogle Scholar
  • 2c Kumar Y, Prasad M, and Misra S. inventors; WO  2003014060. 
    Crossref
  • 2d Kankan RN, and Rao DR. inventors; WO  2005061432. 
    Crossref
  • 2e Srinivas K. Srinivasan N. Reddy KS. Ramakrishna M. Reddy CR. Arunagiri M. Kumari RL. Venkatarman S. Mathad VT. Org. Process Res. Dev.  2005,  9:  314 
    CrossrefGoogle Scholar
  • 2f Venkataraman S, Mathad VT, Reddy KS, Srinivasan N, Reddy CR, Arunagiri M, and Kumari RL. inventors; US  20060094904. 
    Crossref
  • 2g Toplak R. inventors; WO  2006066931. 
    Crossref
  • 2h Turchetta S, Ciambecchini U, and Massardo P. inventors; US  20060079716. 
    Crossref
  • 3a Anderson PG. Schink HE. Osterlund K. J. Org. Chem.  1998,  63:  8067 
    CrossrefGoogle Scholar
  • 3b Colombo L, Rossi R, Castaldi G, and Allegrini P. inventors; CA  2502640. 
    Crossref
  • 3c Hedberg C. Anderson PG. Adv. Synth. Catal.  2005,  347:  662 
    CrossrefGoogle Scholar
  • 3d Chen G. Tokunaga N. Hayashi T. Org. Lett.  2005,  7:  2285 
    CrossrefGoogle Scholar
  • 3e Ulgheri F. Marchetti M. Piccolo O. J. Org. Chem.  2007,  72:  6056 
    CrossrefGoogle Scholar
  • 4 De Castro KA. Ko J. Park D. Park S. Rhee H. Org. Process Res. Dev.  2007,  5:  918 
    Google Scholar
  • 5 De Luca L. Giacomelli G. Porcheddu A. Org. Lett.  2002,  4:  553 
    CrossrefGoogle Scholar
  • 6 Sereda GA. Tetrahedron Lett.  2004,  45:  7265 
    CrossrefGoogle Scholar
  • 7a Martinelli MJ. Nayyar NK. Moher ED. Dhokte UP. Pawlak JM. Vaidyanathan R. Org. Lett.  1999,  1:  447 
    CrossrefGoogle Scholar
  • 7b Choudary BM. Chowdari NS. Kantam ML. Tetrahedron  2000,  56:  7291 
    CrossrefGoogle Scholar
  • 7c Martinelli MJ. Vaidyanathan R. Pawlak JM. Nayyar NK. Dhokte UP. Doecke CW. Zollars LMH. Moher ED. Khau VV. Kosmrlj B. J. Am. Chem. Soc.  2002,  124:  3578 
    CrossrefGoogle Scholar
  • 7d Das B. Reddy VS. Reddy MR. Tetrahedron Lett.  2004,  45:  6717 
    CrossrefGoogle Scholar
  • 7e Fazaeli R. Tangestaninejad S. Aliyan H. Can. J. Chem.  2006,  84:  812 
    CrossrefGoogle Scholar
  • 8 Kolb HC. Van Nieuwenhze MS. Sharpless KB. Chem. Rev.  1994,  94:  2483 
    Google Scholar
  • 10 Iovel I. Mertins K. Kischel J. Zapf A. Beller M. Angew. Chem. Int. Ed.  2005,  44:  3913 
    CrossrefPubMedGoogle Scholar
  • 11 Heydari A. Khaksar S. Akbari J. Esfandyari M. Pourayoubi M. Tajbakhsh M. Tetrahedron Lett.  2007,  48:  1135 
    CrossrefGoogle Scholar
  • 12 Li A. Kindelin PJ. Klump DA. Org. Lett.  2006,  8:  1233 
    CrossrefPubMedGoogle Scholar
  • 13 Li D. Guo Y. Ding Y. Xiao W. Chem. Commun.  2006,  799 
    CrossrefGoogle Scholar
  • 14 Razzetti G, Mantegazza S, Rossi R, and Allegrini P. inventors; EP  20060823. 
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The flash column chromatography may be avoided by using crystallization. This is for industrial consideration.