Anacetrapib
A hidden solvent impurity turns out to enable a scalable, chromatography-free synthesis of the anacetrapib biaryl core (J Org Chem 2011)
Original 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
This paper reports the discovery that a low-level solvent impurity has a remarkable, previously unrecognized effect on a ruthenium-catalyzed direct arylation reaction used to build the biaryl core of anacetrapib. Identifying and understanding this impurity effect allowed development of a robust, high-yield arylation protocol, demonstrated on a multikilogram scale using a carboxylate cocatalyst. The resulting process provides a practical, scalable, and chromatography-free route to the biaryl core structure central to anacetrapib, offering a more manufacturable synthesis than earlier methods.
Original 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.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.