title: Preparative scale synthesis of the biaryl core of anacetrapib via a ruthenium-catalyzed direct arylation reaction: unexpected effect of solvent impurity on the arylation reaction.
abstract: In this report, we disclose our findings regarding the remarkable effect of a low-level impurity found in the solvent used for a ruthenium-catalyzed direct arylation reaction. This discovery allowed for the development of a robust and high-yield arylation protocol that was demonstrated on a multikilogram scale using carboxylate as the cocatalyst. Finally, a practical, scalable, and chromatography-free synthesis of the biaryl core of Anacetrapib is described.
authors.affiliation: Department of Process Research, Merck Frosst Canada, Kirkland, Quebec, Canada. stephane_ouellet@merck.com
authors.forename: Stéphane G
authors.initials: SG
authors.lastname: Ouellet
authors.forename: Amélie
authors.initials: A
authors.lastname: Roy
authors.forename: Carmela
authors.initials: C
authors.lastname: Molinaro
authors.forename: Rémy
authors.initials: R
authors.lastname: Angelaud
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Marcoux
authors.forename: Paul D
authors.initials: PD
authors.lastname: O'Shea
authors.forename: Ian W
authors.initials: IW
authors.lastname: Davies
mesh_terms: D002384:Catalysis; D015394:Molecular Structure; D023303:Oxazolidinones / Q000138:chemical synthesis* / Q000737:chemistry; D012428:Ruthenium / Q000737:chemistry*; D012997:Solvents / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: D023303:Oxazolidinones; D012997:Solvents; D012428:Ruthenium; C530884:anacetrapib