Stephanie C. Kosnik, Zeno Leuter, Kevin Schwickert
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引用次数: 0
Abstract
Spherical crystallization is a widely used technique for the preparation of spherically shaped agglomerates of crystalline material, which results in free-flowing powders with improved micromeritic properties. In this study, we applied this technique to the reactive crystallization of 3-iodo-7-methyl-1H-indazole, a critical early intermediate for one of our Active Pharmaceutical Ingredients at Boehringer Ingelheim. We utilized a traditional spherical agglomeration approach to identify a bridging liquid that could be easily implemented into the current crystallization process. Our experiments showed that the amount and rate of antisolvent addition were important for the crystallization; however, the stir rate and the amount of bridging liquid were the most critical factors. We successfully scaled up this process to a 300 L pilot plant reactor, keeping a constant power per unit mass during scale-up. The results showed that the spherical crystallizations for both 300 L batches were highly successful with almost identical particle sizes.
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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