Process Research and Development for the Production of Intermediates for the Synthesis of Carbocyclic Nucleosides

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• 作者：Robin Bannister ; Chris Hanson ; Neil Henderson ; Ray McCague ; and Graham Ruecroft
• 刊名：Organic Process Research & Development
• 出版年：1997
• 出版时间：November 1997
• 年：1997
• 卷：1
• 期：6
• 页码：415 - 419
• 全文大小：147K
• 年卷期：v.1,no.6(November 1997)
• ISSN：1520-586X

文摘

The synthesis of[3aR,4S,6R,6aS]-6-amino-N-ethyltetrahydro-2,2-dimethyl-4H-cyclopenta-1,3-dioxole-4-carboxamide, akeysingle enantiomer intermediate to carbocyclic nucleosidessuchas adenosine agonists, is reported involving a scalablecatalyticosmium 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 withanhydrousethylamine to give the carbocyclic key intermediate. Therateof this known reaction, carried out in a pressure vessel,isconsiderably enhanced by acid catalysis usingethylammoniumion. In addition, the need for a pressure vessel iscircumventedby using anhydrous ethylamine with acid catalysis.Alternatively stoichiometric ethylammonium ion in an appropriatecosolvent can be used to form the key intermediate in highyield.