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Synthesis 2012(6): 875-880  
DOI: 10.1055/s-0031-1289724
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

A Multikilogram-Scale Synthesis of (R)-Methyl 2-[(1r,4R)-4-(tert-Butoxy­carbonylamino)cyclohexyl]-2-(2-nitrophenylsulfonamido)acetate - A Doubly Protected Building Block with Three Points of Variation

Gregory Carr*a, Sam Butterwortha, Phil Walkera, Folkert Reckb, Bolin Gengb, Lakshmipathi Pandarinathanb
a Astrazeneca Pharmaceuticals, Alderley Park, Macclesfield, Cheshire, SK10 4TG, UK
b Infection Innovative Medicines Unit, AstraZeneca R & D Boston, 35 Gatehouse Drive, Waltham, MA 02451, USA
Fax: +44(1625)513910; e-Mail: greg.carr@astrazeneca.com;
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Publikationsverlauf

Received 19 October 2011
Publikationsdatum:
27. Februar 2012 (online)

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Abstract

A robust and scalable synthesis of (R)-methyl 2-[(1r,4R)-4-(tert-butoxycarbonylamino)cyclohexyl]-2-(2-nitrophenylsulfon­amido)acetate is reported. This serves as a scaffold for the preparation of trans-substituted aminocyclohexanes. The key synthetic step is the reduction of d-4-hydroxyphenylglycine, or a protected equivalent, to achieve the required regiochemistry across the cyclohexyl ring.

Key words

chirality - diastereoselectivity - hydrogenation - protecting groups - reduction

    References

  • 1a Levin JI, Chen JM, Cole DC, Du MT, and Laakso LM. inventors; US Patent Appl. Publ. US  6225311.  ; Chem. Abstr. 2001, 134, 326767
  • 1b Levin JI, Chen JM, and Cole DC. inventors; Patent PCT Int. Appl. WO  2000044709.  ; Chem. Abstr. 2000, 133, 150908
  • 2a Semple JE, Brunck TK, Levy OE, and Tamura SY. inventors; Patent PCT Int. Appl. WO  2001027141.  ; Chem. Abstr. 2001, 134, 311435
  • 2b Scarborough RM, Marlowe CK, and Zhu B. inventors; US Patent Appl. Publ. US  6211154.  ; Chem. Abstr. 2001, 134, 266567
  • 2c Scarborough RM, Marlowe CK, and Zhu B. inventors; US Patent Appl. Publ. US  6022861.  ; Chem. Abstr. 2000, 132, 137734
  • 3a Cronin M, Geng B, and Reck F. inventors; Patent PCT Int. Appl. WO  2010055348.  ; Chem. Abstr. 2010, 152, 592011
  • 3b Hubschwerlen C, Rueedi G, Surivet J, and Zumbrunn Acklin C. inventors; Patent PCT Int. Appl. WO  2009147616.  ; Chem. Abstr. 2009, 152, 37571
  • 3c Hubschwerlen C, Rueedi G, Surivet J, and Zumbrunn Acklin C. inventors; Patent PCT Int. Appl. WO  2008078305.  ; Chem. Abstr. 2008, 149, 153099
  • 4 Tullis JS. Laufersweiler MJ. VanRens JC. Natchus MG. Bookland RG. Almstead NG. Pikul S. De B. Hsieh LC. Janusz MJ. Branch TM. Peng SX. Jin YY. Hudlicky T. Oppong K. Bioorg. Med. Chem. Lett.  2001,  11:  1975 
    Suche in Google Scholar
  • 5 Parmee ER. He J. Mastracchio A. Edmondson SD. Colwell L. Eiermann G. Feeney WP. Habulihaz B. He H. Kilburn R. Leiting B. Lyons K. Marsilio F. Patel RA. Petrov A. Di Salvo J. Wu JK. Thornberry NA. Weber AE. Bioorg. Med. Chem. Lett.  2004,  14:  43 
    Suche in Google Scholar
  • 6 Banfi A. Benedini F. Casanova G. Perego R. Toma L. Synth. Commun.  1989,  19:  1787 
    Suche in Google Scholar
  • 7 Hirai Y. Yokota K. Momose T. Heterocycles  1994,  39:  603 
    Suche in Google Scholar
  • 8 Hulin B, Parker JC, and Piotrowski DW. inventors; US Patent Appl. Publ. US  20050234065.  ; Chem. Abstr. 2005, 143, 406151
  • 9 Slade JS. Vivelo JA. Parker DJ. Bajwa J. Liu H. Girgis M. Parker DT. Repic O. Blacklock T. Org. Process Res. Dev.  2005,  9:  608 
    Suche in Google Scholar
  • 10 For alternative preparations of 12, see: Ohta Y. Terada K. Masuda T. Sanda F. Heterocycles  2009,  78:  1477 
    Suche in Google Scholar
  • 11 Vaultier M. Knouzi N. Carrie R. Tetrahedron Lett.  1983,  24:  763 
    Suche in Google Scholar
  • 12 Greene TW. Wuts PGM. Protective Groups in Organic Synthesis   3rd ed.:  Wiley-Interscience; New York: 1999. 
    Suche in Google Scholar
  • 13 Turner JJ. Sikkema FD. Filippov DV. van der Marel GA. van Boom JH. Synlett  2001,  1727 
  • 14 Bretherick’s Handbook of Reactive Chemical Hazards   Vol. 1-2, 7th ed.:  Urben P. Elsevier; Amsterdam: 2007.