Reactive resin facilitated preparation of an enantiopure fluorobicycloketone

Autor:	David L. Hughes, Derek W. Henderson, Enrique Vazquez, Christopher J. Welch, Ian W. Davies, Audrey Wong, Jeffrey T. Kuethe, Mohamed Shaimi
Rok vydání:	2004
Předmět:	Chiral column chromatography Enantiopure drug Cyclopropanation Ligand Chemistry Intramolecular force Organic Chemistry Enantioselective synthesis Organic chemistry Physical and Theoretical Chemistry Biochemistry Chloroketone Catalysis
Zdroj:	Organic & Biomolecular Chemistry. 2:168
ISSN:	1477-0539 1477-0520
DOI:	10.1039/b312180c
Popis:	A facile preparation of enantiopure ethyl (1S,5S,6S)-6-fluoro-2-oxobicyclo[3.1.0]hexane-6-carboxylate 1 is described. The key feature of the synthesis involves copper-catalyzed enantioselective intramolecular cyclopropanation of a diazoketone to form endo-fluorocyclopropane 1 in a single operation. Removal of a problematic chloroketone impurity using a reactive resin treatment enabled a high throughput enantiopurity upgrade by chiral HPLC. The development of a scalable synthesis of 1 is presented, including details of the selection of catalyst and ligand optimization, incorporation of a reactive resin treatment and selection of chiral HPLC media and conditions.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a76bb003a4b792608b290070e57797ff https://doi.org/10.1039/b312180c Zobrazit plný text záznamu