R. Bannister, Chris Hanson, Neil Henderson
Nov 14, 1997
Citations
0
Influential Citations
4
Citations
Journal
Organic Process Research & Development
Abstract
The synthesis of [3aR,4S,6R,6aS]-6-amino-N-ethyltetrahydro-2,2-dimethyl-4H-cyclopenta-1,3-dioxole-4-carboxamide, a key single enantiomer intermediate to carbocyclic nucleosides such as adenosine agonists, is reported involving a scalable catalytic osmium tetraoxide dihydroxylation of (−)-2-azabicyclo[2.2.1]hept-5-en-3-one. The acetonide-protected diol [3aS,4R,7S,7aR]-tetrahydro-2,2-dimethyl-4,7-methano-1,3-dioxolo[4,5-c]pyridin-6(3aH)-one is subject to lactam ring opening with anhydrous ethylamine to give the carbocyclic key intermediate. The rate of this known reaction, carried out in a pressure vessel, is considerably enhanced by acid catalysis using ethylammonium ion. In addition, the need for a pressure vessel is circumvented by using anhydrous ethylamine with acid catalysis. Alternatively stoichiometric ethylammonium ion in an appropriate cosolvent can be used to form the key intermediate in high yield.