John L. Tucker*, David J. Kucera, Don Hettinger, Shawn Branum, Brian Cochran, Jeff Culhane, Lucy Zhao, Andrew Benjamin Palmer, Kyle Leeman, Stanley Yu, Bénédicte Martin, Nicolas André, Julien Perron, Horacio Comas and Yuxin Zhao,
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Efficiency and Sustainability through Development of a Next-Generation, Commercial Synthesis of Valbenazine Ditosylate
The synthetic process used to manufacture valbenazine ditosylate (API of INGREZZA) has proven to be highly selective and robust, but opportunities remain for greener chemistry performance and continuous improvement enabled via simplification of process operations by truncating the manufacturing time and by reducing the overall process waste and environmental footprint during the first three most critical transformations. Neurocrine’s next-generation commercial process was developed encompassing principles of Pharmaceutical Green Chemistry ( Org. Process Res. Dev.2006, 10, 315−319) and employs strategies for accelerated reaction kinetics, simplified reaction medium, and elimination of unnecessary workup procedures for greater process efficiency and operational agility. The new, greener process has delivered greater efficiency and sustainability by reducing the time of manufacture by 43% and reducing material use by 45% while concomitantly improving the overall process yield by 5% and reducing water use by 32%.
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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