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Double Heck Route to a Dibenzoxepine and Convergent Suzuki Cross-Coupling Strategy for the Synthesis of an MR Antagonist

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journal contribution
posted on 19.12.2016 by Marvin M. Hansen, Neil J. Kallman, Thomas M. Koenig, Ryan J. Linder, Rachel N. Richey, John R. Rizzo, Jeffrey A. Ward, Hannah Yu, Tony Y. Zhang, David Mitchell
A practical pilot plant convergent synthesis of MR antagonist LY2623091 was established. For synthesis convergence, a vinyl bromide geometric isomer and chiral alaninol derivative were required building blocks. Key to the synthesis route development is a stereoselective synthesis of the E-vinyl bromide via a sequential double Heck reaction, Suzuki–Miyaura cross-coupling of the vinyl bromide, a selective nitro reduction, and a highly sensitive cyanamide hydrolysis to the urea. Improvements in yield and processing were accomplished by two sets of telescoping methods which decreased the manufacturing time and provided purity enhancements.