Download PDF
Synthesis 2003(3): 0403-0407
DOI: 10.1055/s-2003-37362
PAPER
© Georg Thieme Verlag Stuttgart · New York

Mono-Chlorination of Electron-Rich Arylalkyl- and Heteroarylalkyl-amines and Amino Acids Using Sulfuryl Chloride

Guixue Yu*a, Helen J. Masona, Kim Galdia, Ximao Wua, Lyndon Corneliusa, Ning Zhaob, Michael Witkusb, William R. Ewinga, John E. Macora
a Discovery Chemistry, Bristol-Myers Squibb, P.O. Box 5400, Princeton, NJ 08543-5400, USA
Fax: +1(609)8183450; e-Mail: guixue.yu@bms.com;
b Preclinical Candidate Optimization, Bristol-Myers Squibb, P.O. Box 5400, Princeton, NJ 08543-5400, USA
Further Information

Publication History

Received 11 October 2002
Publication Date:
19 February 2003 (online)

    Permissions and Reprints All articles of this category

Abstract

Sulfuryl chloride has been used to mono-chlorinate electron-rich arylalkyl- and heteroarylalkyl-amines and amino acids in a mild and efficient one-pot transformation with straightforward purification­. Protection of the amines was not needed, and racemization of the chiral amino acids was minimal.

Key words

halogenation - chlorination - sulfuryl chloride - amino acids - amines

    References

  • 1a Nicolaou KC. Boddy CNC. Brase S. Winssinger N. Angew. Chem. Int. Ed.  1999,  38:  2097 
    Google Scholar
  • 1b Koyama M. Kodama Y. Tsuruoka T. Ezaki N. Niwa T. Inouye S. J. Antibiot.  1981,  34:  1569 
    Google Scholar
  • 1c Gribble GW. Environ. Sci. Technol.  1994,  28:  310 
    Google Scholar
  • 2a Crast LB, and Gottstein WJ. inventors; US Patent  516047. 
    Crossref
  • 2b Cossy J. Molina JL. Desmurs JR. Tetrahedron Lett.  2001,  42:  5713 
    CrossrefGoogle Scholar
  • 2c Elslager EF. Worth DF. J. Med. Chem.  1967,  10:  971 
    CrossrefGoogle Scholar
  • 3 March J. Smith MB. Advanced Organic Chemistry, Reactions, Mechanisms and Structure   Wiley; New York: 2001.  p.704-707  ; and references cited therein
    Google Scholar
  • 4a Charifson PS. Wyrick SD. Hoffman AJ. Simmons RMA. Bowen JP. McDougald DL. Mailman RB. J. Med. Chem.  1988,  31:  1941 
    CrossrefPubMedGoogle Scholar
  • 4b Watanabe N. Kabasawa Y. Takase Y. Matsukura M. Miyazaki K. Ishihara I. J. Med. Chem.  1998,  41:  3367 
    CrossrefPubMedGoogle Scholar
  • 5a Chumpradit S. Kung HF. Billings J. Kung M. Pan S. J. Med. Chem.  1989,  32:  1431 
    Google Scholar
  • 5b Nishiyama S. Suzuki Y. Yamamura S. Tetrahedron Lett.  1988,  29:  559 
    Google Scholar
  • 5c Wyrick SD. Mailman RB. J. Labelled Compd. Radiopharm.  1985,  22:  189 
    Google Scholar
  • 6a Watson WD. J. Org. Chem.  1985,  50:  2145 
    Google Scholar
  • 6b Smith K. Tzimas M. Brown CM. Payne K. Sulfur Lett.  1999,  22:  89 
    Google Scholar
  • 6c Reiter L. Berg GE. Heterocycles  1992,  34:  771 
    Google Scholar
  • 6d Godt HC. Wann RE. J. Org. Chem.  1962,  27:  1459 
    Google Scholar
  • 6e Unterhalt B. Hanewacker GA. Arch. Pharm.  1989,  322:  389 
    Google Scholar
  • 7a Yu G, Macor JE, Chung H.-J, Humora M, Katipally K, Wang Y, and Kim S. inventors; Patent application WO  0056719. 
  • 7b Yu G. Mason HJ. Wu X. Endo M. Douglas J. Macor JE. Tetrahedron Lett.  2001,  42:  3247 
    Google Scholar
  • 7c Endo M. Douglas J. Synth Commun.  2000,  30:  2609 
    Google Scholar
  • 9a Rao AVR. Chakraborty TK. Reddy KL. Rao AS. Tetrahedron Lett.  1994,  35:  5043 
    CrossrefGoogle Scholar
  • 9b Renault O. Dallemagne P. Rault S. Org. Prep. Proced. Int.  1997,  29:  488 
    CrossrefGoogle Scholar
8

Chiral purity (ee%) was determined by chiral HPLC. Specific conditions were: 9 and 10 used Chiralcel OD-H with heptane-i-PrOH-Et2NH (95:5:0.1) at a flow rate of 0.8 mL/min; 11 and 12 used Chiralpak AD with heptane-i-PrOH-Et2NH (98:2:0.1) at a flow rate of 1.0 mL/min, 13 and 14 used Chiralpak OJ with heptane-MeOH-EtOH-Et2NH (85:7.5:7.5:0.1) at a flow rate of 1.0 mL/min; 15 and 16 used Chiralpak AD with heptane-i-PrOH-Et2NH (95:5:0.1 v/v/v) at a flow rate of 1.0 mL/min.