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

Vilius Franckevičius; Kristian Rahbek Knudsen; Mark Ladlow; Deborah A. Longbottom; Steven V. Ley

doi:10.1055/s-2006-939036

LETTER

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

Vilius Franckevičius^a, Kristian Rahbek Knudsen^a, Mark Ladlow^b, Deborah A. Longbottom^a, 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

Abstract

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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-Cube^TM (a continuous-flow reactor employing a mixed hydrogen-liquid flow stream)

Key words

tetrazole - asymmetric - synthesis - organocatalysis - flow - hydrogenation

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References

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