Sri Krishna Nimmagadda, Srinivas Kalidindi, Siva Sankar Bondigela, Satish Korapati, Debottam Dasgupta, Noormohamed Abdul Malik, Prakasa Rao, Prantik Maity, John R. Coombs, Michael Hay, Eric M. Simmons, Sabuj Mukherjee, Rajappa Vaidyanathan, Martin D. Eastgate, Francisco González-Bobes
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引用次数: 0
Abstract
We report herein the development and scale up of an Ir-catalyzed N-alkylation reaction between a 4-bromopyridin-2-amine (1) and (4-(5-(1,1-difluoroethyl)-1,2,4-oxadiazol-3-yl)bicyclo[2.2.2]octan-1-yl)methanol (2) proceeding via a borrowing hydrogen process. The traditional approach of alcohol oxidation followed by reductive amination posed challenges that are attributed to the poor nucleophilicity of the 2-aminopyridine derivative (1) resulting in lower isolated yields. Several catalysts and bases were evaluated for the successful N-alkylation of 1 with 2, and an Ir (III) catalyst in combination with LiOt-Bu as a base was found to provide optimal conversion. The borrowing hydrogen process was successfully demonstrated on a 1.5 kg scale and afforded >70% yield of 3 without the need for a sealed reactor or any other specialized equipment.
期刊介绍：
The journal Organic Process Research & Development serves as a communication tool between industrial chemists and chemists working in universities and research institutes. As such, it reports original work from the broad field of industrial process chemistry but also presents academic results that are relevant, or potentially relevant, to industrial applications. Process chemistry is the science that enables the safe, environmentally benign and ultimately economical manufacturing of organic compounds that are required in larger amounts to help address the needs of society. Consequently, the Journal encompasses every aspect of organic chemistry, including all aspects of catalysis, synthetic methodology development and synthetic strategy exploration, but also includes aspects from analytical and solid-state chemistry and chemical engineering, such as work-up tools，process safety, or flow-chemistry. The goal of development and optimization of chemical reactions and processes is their transfer to a larger scale; original work describing such studies and the actual implementation on scale is highly relevant to the journal. However, studies on new developments from either industry, research institutes or academia that have not yet been demonstrated on scale, but where an industrial utility can be expected and where the study has addressed important prerequisites for a scale-up and has given confidence into the reliability and practicality of the chemistry, also serve the mission of OPR&D as a communication tool between the different contributors to the field.
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