PDF herunterladen
Synlett 2011(10): 1454-1458  
DOI: 10.1055/s-0030-1260584
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Highly Efficient Carbamate Formation from Alcohols and Hindered Amino Acids or Esters Using N,N′-Disuccinimidyl Carbonate (DSC)

Hongmei Li*, Cheng-yi Chen, Jaume Balsells Padros
Department of Process Research, Merck Research Laboratories, P.O. Box 2000, Rahway, NJ 07065-0900, USA
Fax: +1(732)5941499; e-Mail: hongmei_li@merck.com;
Weitere Informationen

Publikationsverlauf

Received 7 February 2011
Publikationsdatum:
26. Mai 2011 (online)

   Lizenzen und Reprints Alle Artikel dieser Rubrik
Preview

Abstract

A highly efficient and straightforward protocol to prepare carbamates from alcohols and hindered amino acids/esters mediated by N,N′-disuccinimidyl carbonate (DSC) in the presence of catalytic amount of pyridine is described. This method could be carried out under mild conditions in one pot, and a wide variety of carbamates were obtained in high yield with excellent purity.

Key words

carbamate - N,N′-disuccinimidyl carbonate - DSC - hindered amino acids/esters - pyridine

    References and Notes

  • 1a Adams P. Baron FA. Chem. Rev.  1965,  65:  567 
    Suche in Google Scholar
  • 1b Ray S. Chaturvedi D. Drugs Future  2004,  29:  343 
    Suche in Google Scholar
  • 1c Ray S. Pathak SR. Chaturvedi D. Drugs Future  2005,  30:  161 
    Suche in Google Scholar
  • 1d Mateen A. Chapalamadugu S. Kashar B. Bathi AR. Chaudhary GR. Biol. Degrad. Biorem. Toxic. Chem.  1994,  198 
  • 1e Wigfield YY. Food Sci. Technol. (NY)  1996,  77:  1501 
    Suche in Google Scholar
  • 2a McCauley JA. McIntyre CJ. Rudd MT. Nguyen KT. Romano JJ. Butcher JW. Gilbert KF. Bush KJ. Holloway K. Swestock J. Wan B. Carroll SS. DiMuzio JM. Graham DJ. Ludmerer SW. Mao S. Stahlhut MW. Fandozzi CM. Trainor N. Olsen DB. Vacca JP. Liverton NJ. J. Med. Chem.  2010,  53:  2443 
    Suche in Google Scholar
  • 2b Liverton NJ. Carroll SS. DiMuzio J. Fandozzi C. Graham DJ. Hazuda D. Holloway K. Ludmerer SW. McCauley JA. McIntyre CJ. Olsen DB. Rudd MT. Stahlhut M. Vacca JP. Antimicrob. Agents Chemother.  2010,  54:  305 
    Suche in Google Scholar
  • 2c Holloway MK, Liverton NJ, Ludmerer SW, McCauley JA, Olsen DB, Rudd MT, Vacca JP, and McIntyre CJ. inventors; US  7,470,664. 
  • 2d Belyk KM. Xiang B. Bulger PG. Leonard WR. Balsells J. Yin J. Chen C. Org. Process Res. Dev.  2010,  14:  692 
    Suche in Google Scholar
  • 3a Montalbetti CAGN. Falque V. Tetrahedron  2005,  61:  10827 
    Suche in Google Scholar
  • 3b D’Addona D. Bochet CG. Tetrahedron Lett.  2001,  42:  5227 
    Suche in Google Scholar
  • 3c Grzyb JA. Shen M. Yoshina-Ishii C. Chi W. Brown RS. Batey RA. Tetrahedron  2005,  61:  7153 
    Suche in Google Scholar
  • 3d Batey RA. Yoshina-Ishii C. Taylor SD. Santhakumar V. Tetrahedron Lett.  1999,  40:  2669 
    Suche in Google Scholar
  • 3e Grzyb JA. Batey RA. Tetrahedron Lett.  2008,  49:  5279 
    Suche in Google Scholar
  • 3f Davulcu AH. McLeod DD. Li J. Katipally K. Littke A. Doubleday W. Xu Z. McConlogue CW. Lai CJ. Gleeson M. Schwinden M. Parsons RL.
    J. Org. Chem.  2009,  74:  4068 
    Suche in Google Scholar
  • 4 Ghosh AK. Duong TT. McKee SP. Thompson WJ. Tetrahedron Lett.  1992,  33:  2781 
    CrossrefSuche in Google Scholar
  • 5a Diamanti S. Arifuzzaman S. Elsen A. Genzer J. Vaia RA. Polymer  2008,  49:  3770 
    Suche in Google Scholar
  • 5b Hamilton GA. Backes BJ. Tetrahedron Lett.  2006,  47:  967 
    Suche in Google Scholar
  • 5c Alsina J. Rabanal F. Chiva C. Giralt E. Albericio F. Tetrahedron  1998,  54:  10125 
    Suche in Google Scholar
  • 7 Ototake N. Nakamura M. Dobashi Y. Fukaya H. Kitagawa O. Chem. Eur. J.  2009,  15:  5090 
    CrossrefSuche in Google Scholar
6

General Procedure for Preparation of Carbamate 4 To a solution of alcohol 5 (0.5 g, 3.9 mmol) in anhyd DMF (3 mL) was added DSC (1.2 g, 1.2 equiv) and pyridine (63 µL, 0.2 equiv). The mixture was heated and aged at 40 ˚C
for 15 h until complete activation of 5 was observed as monitored by GC (>99% conversion). The mixture was cooled to ambient temperature for addition of H2O (3 mL), keeping temperature below 30 ˚C. l-tert-Leucine (0.53 g, 1.0 equiv) and K3PO4 (1.66 g, 2 equiv), keeping the reaction temperature below 30 ˚C. The reaction mixture was then stirred at ambient temperature for 3-6 h until complete carbamate formation was observed as monitored by HPLC or TLC. To the reaction mixture was charged H2O (10 mL) and EtOAc (10 mL). The organic layer was separated, and the aqueous layer was extracted with EtOAc (5 mL). Both organic layers were combined, washed sequentially with 1 N HCl, H2O and brine, and dried (MgSO4). Concentration of the organic solution afforded the carbamate 4 as an oil, amide rotamers exists by NMR spectrum. ¹H NMR (500 MHz, CDCl3): δ = 0.93 (s, 6 H), 1.05 (s, 9 H), 1.35-1.38 (m, 2 H), 2.01-2.06 (m, 2 H), 3.80-3.82 (d, J = 10.0 Hz, 1 H), 3.87-3.89 (d, J = 10.0 Hz, 1 H), 3.98 (br, 0.3 H, minor rotamer), 4.21-4.23 (d, J = 10.0 Hz, 0.7 H, major rotamer), 4.93-4.95 (d, J = 10.0 Hz, 1 H), 5.01-5.04 (d, J = 15.0 Hz, 1 H), 5.27-5.29 (d, J = 10.0 Hz, 0.7 H, major rotamer), 5.78-5.86 (m, 1 H), 6.21-6.22 (br, 0.3 H, minor rotamer). ¹³C NMR (125 MHz, CDCl3): δ = 24.1, 24.3 (minor rotamer), 26.5, 26.9 (minor rotamer), 28.30, 34.0, 34.6, 38.2, 62.0, 63.3 (minor rotamer), 73.2, 73.9 (minor rotamer), 114.1, 139.2, 139.9 (minor rotamer), 156.7, 176.4, 177.2 (minor rotamer).