Synlett 2006(6): 889-892  
DOI: 10.1055/s-2006-939036
LETTER
© Georg Thieme Verlag Stuttgart · New York

Practical Synthesis of (S)-Pyrrolidin-2-yl-1H-tetrazole, Incorporating Efficient Protecting Group Removal by Flow-Reactor Hydrogenolysis

Vilius Franckevičiusa, Kristian Rahbek Knudsena, Mark Ladlowb, Deborah A. Longbottoma, Steven V. Ley*a
a University of Cambridge, Department of Chemistry, Lensfield Road, Cambridge, CB2 1EW, UK
Fax: +44(1223)336442; e-Mail: svl1000@cam.ac.uk;
b GlaxoSmithKline Cambridge Technology Centre, University of Cambridge, Cambridge, CB2 1EW, UK
Further Information

Publication History

Received 6 February 2006
Publication Date:
14 March 2006 (eFirst)

Abstract

A practical, safe, high-yielding and efficient synthesis of (S)-pyrrolidin-2-yl-1H-tetrazole has been developed, which avoids the generation of ammonium azide in the cyclisation step and the use of a 9:1 acetic acid-water mixture as the solvent in the ­hydrogenation. The previously extended hydrogenolysis reaction time (three days) is now reduced to hours through the use of an H-CubeTM (a continuous-flow reactor employing a mixed hydrogen-liquid flow stream)

    References and Notes

  • 1 Cobb AJA. Shaw DM. Ley SV. Synlett  2004,  558 
  • 2 Cobb AJA. Shaw DM. Longbottom DA. Gold JB. Ley SV. Org. Biomol. Chem.  2005,  3:  84 
  • 3 Torii H. Nakadai M. Ishihara K. Saito S. Yamamoto H. Angew. Chem. Int. Ed.  2004,  43:  1983 
  • 4 Hartikka A. Arvidsson PI. Tetrahedron: Asymmetry  2004,  15:  1831 
  • 5 Cobb AJA. Longbottom DA. Shaw DM. Ley SV. Chem. Commun.  2004,  1808 
  • 6 Mitchell CET. Brenner SE. Ley SV. Chem. Commun.  2005,  5346 
  • 7 Ramachary DB. Barbas CF. Org. Lett.  2005,  7:  1577 
  • 8 Momiyama N. Torii H. Saito S. Yamamoto H. Proc. Natl. Acad. Sci. U.S.A.  2004,  101:  5374 
  • 9 Suri JT. Ramachary DB. Barbas CF. Org. Lett.  2005,  7:  1383 
  • 10 Thayumanavan NR. Tanaka F. Barbas CF. Org. Lett.  2004,  3541 
  • 11 Chowdari NS. Barbas CF. Org. Lett.  2005,  7:  867 
  • 12 Knudsen KR. Mitchell CET. Ley SV. Chem. Commun.  2006,  66 
  • 13 Kumarn S. Shaw DM. Longbottom DA. Ley SV. Org. Lett.  2005,  7:  4189 
  • 14 Marigo M. Jørgensen KA. Chem. Commun.  2006,  in press 
  • 15 Almquist RG. Chao WR. Jennings-White C. J. Med. Chem.  1985,  28:  1067 
  • 16 Hartikka A. Arvidsson PI. Eur. J. Org. Chem.  2005,  4287 
  • 17 Koguru K. Oga T. Mitsui S. Orita R. Synthesis  1998,  910 
  • 18 Saaby S. Knudsen KR. Ladlow M. Ley SV. Chem. Commun.  2005,  2909 
  • 19 Jones RV. Godorhazy L. Varga N. Szalay D. Urge L. Darvas F. J. Comb. Chem.  2006,  8:  110 
  • 20 Desai B. Kappe O. J. Comb. Chem.  2005,  7:  641 
21

For further details, please refer to the product details on the company website: http://www.thalesnano.com. Address: Thales Nanotechnology, 1031 Budapest, Záhony ucta 7 (Graphisoft Park), Hungary. Fax: +36(1)6666190; Tel: +36(1)6666100.