174642-99-0Relevant articles and documents
Asymmetric Synthesis of the Cyclohexyl Fragment in RORγt Inhibitor (BMS-986251) Enabled by a Dynamic Kinetic Resolution of Hageman's Ester
Coombs, John R.,Gallagher, William P.,González-Bobes, Francisco,Guerrero, Carlos A.,Joe, Candice L.,Katipally, Kishta,Mudryk, Boguslaw M.,Rupasinghe, Sanjeewa,Zhu, Jason
supporting information, (2021/11/30)
The cyclohexyl fragment 1 in BMS-986251 was synthesized starting from Hagemann's ester 2 in 7 steps and 5 isolations. The route is highlighted by a dynamic kinetic resolution (DKR), a telescoped enol nonaflation followed by a palladium-catalyzed carbonylation, and a rhodium-catalyzed directed diastereoselective olefin hydrogenation. The optimized process was demonstrated on 1 kg scale, with an overall 51% yield and >99% ee and dr.