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*aa 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)