title: Reactive resin facilitated preparation of an enantiopure fluorobicycloketone.
abstract: A facile preparation of enantiopure ethyl (1S,5S,6S)-6-fluoro-2-oxobicyclo[3.1.0]hexane-6-carboxylate is described. The key feature of the synthesis involves copper-catalyzed enantioselective intramolecular cyclopropanation of a diazoketone to form endo-fluorocyclopropane 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 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.
authors.affiliation: Department of Process Research, Merck and Co., Inc., PO Box 2000, Rahway, New Jersey 07065, USA. audrey_wong@merck.com
authors.forename: Audrey
authors.initials: A
authors.lastname: Wong
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Welch
authors.forename: Jeffrey T
authors.initials: JT
authors.lastname: Kuethe
authors.forename: Enrique
authors.initials: E
authors.lastname: Vazquez
authors.forename: Mohamed
authors.initials: M
authors.lastname: Shaimi
authors.forename: Derek
authors.initials: D
authors.lastname: Henderson
authors.forename: Ian W
authors.initials: IW
authors.lastname: Davies
authors.forename: David L
authors.initials: DL
authors.lastname: Hughes