title: Practical asymmetric synthesis of a selective endothelin A receptor (ETA) antagonist.
abstract: [structure: see text]. A practical, chromotography-free asymmetric synthesis was developed for the large scale preparation of an endothelin receptor antagonist 2. This synthesis includes a new efficient process for the preparation of 6-bromo-2,3-dihydrobenzofuran, a stereoselective conjugate addition of an aryllithium followed by stereospecific addition of the Grignard reagent of the top aryl bromide, and an aminophosphate-mediated sterospecific intramolecular enolate alkylation, which led to the formation of the five-membered ring bearing three contiguous asymmetric centers.
authors.affiliation: Department of Process Research, Merck Research Laboratories, Rahway, New Jersey 07065, USA. zhiguo_song@merck.com
authors.forename: Z J
authors.initials: ZJ
authors.lastname: Song
authors.forename: M
authors.initials: M
authors.lastname: Zhao
authors.forename: L
authors.initials: L
authors.lastname: Frey
authors.forename: J
authors.initials: J
authors.lastname: Li
authors.forename: L
authors.initials: L
authors.lastname: Tan
authors.forename: C Y
authors.initials: CY
authors.lastname: Chen
authors.forename: D M
authors.initials: DM
authors.lastname: Tschaen
authors.forename: R
authors.initials: R
authors.lastname: Tillyer
authors.forename: E J
authors.initials: EJ
authors.lastname: Grabowski
authors.forename: R
authors.initials: R
authors.lastname: Volante
authors.forename: P J
authors.initials: PJ
authors.lastname: Reider
authors.forename: Y
authors.initials: Y
authors.lastname: Kato
authors.forename: S
authors.initials: S
authors.lastname: Okada
authors.forename: T
authors.initials: T
authors.lastname: Nemoto
authors.forename: H
authors.initials: H
authors.lastname: Sato
authors.forename: A
authors.initials: A
authors.lastname: Akao
authors.forename: T
authors.initials: T
authors.lastname: Mase
mesh_terms: D000959:Antihypertensive Agents / Q000138:chemical synthesis*; D001572:Benzofurans / Q000138:chemical synthesis; D065128:Endothelin Receptor Antagonists; D011725:Pyridines / Q000138:chemical synthesis; D044022:Receptor, Endothelin A
chemical_list: D000959:Antihypertensive Agents; D001572:Benzofurans; D065128:Endothelin Receptor Antagonists; D011725:Pyridines; D044022:Receptor, Endothelin A