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Synthesis 2011(8): 1208-1212  
DOI: 10.1055/s-0030-1259963
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

A Novel Asymmetric Synthesis of cis-(3R,4R)-N-(tert-Butoxycarbonyl)-4-methyl-3-(methylamino)piperidine

Bao-Yu Haoa,c, Jin-Qiang Liu*b, Wei-Han Zhangc, Xin-Zhi Chen*a
a Department of Chemical and Biological Engineering, Zhejiang University, Hangzhou 310027, P. R. of China
Fax: +86(571)87951615; e-Mail: xzchen@zju.edu.cn; e-Mail: liuque.zju@hotmail.com;
b College of Chemistry and Chemical Engineering, Luoyang Normal University, Luoyang 471022, P. R. of China
c Hutchison MediPharma Innovation for Health, Shanghai 201203, P. R. of China
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Publikationsverlauf

Received 23 January 2011
Publikationsdatum:
22. März 2011 (online)

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Abstract

cis-(3R,4R)-N-(tert-Butoxycarbonyl)-4-methyl-3-(meth­ylamino)piperidine, a key intermediate for the synthesis of CP-690550 (a potent protein kinase inhibitor), is prepared via an asymmetric approach starting from ethyl 1-benzyl-3-oxopiperidine-4-carboxylate hydrochloride in an overall yield of 49%. The mild conditions and high yields obtained during the synthesis suggest a potential industrial application for this route.

Key words

asymmetric synthesis - protecting groups - piperidines - protein kinase inhibitor - deoxygenation

    References

  • 1a Blumenkopf TA, Flanagan ME, and Munchhof MJ. inventors; US  6627754.  ; Chem Abstr. 2001, 135, 46193
  • 1b Ruggeri SG, Hawkins JM, Makowski TM, Rutherford JL, and Urban FJ. inventors; WO  2007012953.  ; Chem Abstr. 2007, 146, 206328
  • 2 Brown Ripin DH. Abele S. Cai W. Blumenkopf T. Casavant JM. Doty JL. Flanagan M. Koecher C. Laue KW. McCarthy K. Meltz C. Munchhoff M. Pouwer K. Shah B. Sun J. Teixeira J. Vries T. Whipple DA. Wilcox G. Org. Process Res. Dev.  2003,  7:  115 
    CrossrefGoogle Scholar
  • 3 Cai W. Colony JL. Frost H. Hudspeth JP. Kendall PM. Krishnan AM. Makowski T. Mazur DJ. Phillips J. Brown Ripin DH. Ruggeri SG. Stearns JF. White TD. Org. Process Res. Dev.  2005,  9:  51 
    CrossrefGoogle Scholar
  • 4 Jiang J.-k. Ghoreschi K. Deflorian F. Chen Z. Perreira M. Pesu M. Smith J. Nguyen D.-T. Liu EH. Leister W. Costanzi S. O’Shea JJ. Thomas CJ. J. Med. Chem.  2008,  51:  8012 
    CrossrefGoogle Scholar
  • 5 Frost JM. Bunnelle WH. Tietje KR. Anderson DJ. Rueter LE. Curzon P. Surowy CS. Ji J. Daanen JF. Kohlhaas KL. Buckley MJ. Henry RF. Dyhring T. Ahring PK. Meyer MD. J. Med. Chem.  2006,  49:  7843 
    CrossrefGoogle Scholar
  • 6a Hayashi T. Kawamura N. Ito Y. J. Am. Chem. Soc.  1987,  109:  7876 
    Google Scholar
  • 6b Reetz MT. Gosberg A. Goddard R. Kyung S.-H. Chem. Commun.  1998,  2077 
    Google Scholar
  • 6c Leutenegger U. Madin A. Pfaltz A. Angew. Chem. Int. Ed.  1989,  28:  60 
    Google Scholar
  • 6d von Matt P. Pfaltz A. Tetrahedron: Asymmetry  1991,  2:  691 
    Google Scholar
  • 6e Lin GQ. Chiral Synthesis: Asymmetric Reactions and Applications   Science Press; Beijing: 2005. 
    Google Scholar