Pilot-Scale Continuous Production of LY2886721: Amide Formation and Reactive Crystallization
| Autor: | Patrick M. Pollock, Marvin M. Hansen, Michael Miller, Nikolay Zaborenko, Michael R. Heller, Bradley M. Campbell, Joseph L. Phillips, Molly Harding, Christopher L. Burcham, Christopher S. Polster, Kevin P. Cole, Andrea L. Frederick |
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| Rok vydání: | 2014 |
| Předmět: | |
| Zdroj: | Organic Process Research & Development. 18:1295-1309 |
| ISSN: | 1520-586X 1083-6160 |
| Popis: | The design, development, and implementation of a pilot-scale continuous Schotten–Baumann amide bond formation and reactive crystallization to afford LY2886721 is described. The material met all API quality attributes and was comparable to material produced by a defined batch process. The scalability of the reaction and crystallization processes was confirmed during the development process. The pilot-scale equipment set was contained in a walk-in fume hood and operated at a production rate of 3 kg/day in a 72 h continuous run. Significant technical and business drivers for running the process in continuous flow mode were proposed and examined during development. The continuous process provided for lab hood commercialization and provided for minimal material at risk in the process. The demonstration also confirmed the risk inherent to operation of a tubular reactor under supersaturated conditions, and fouling occurred in the plug flow reactor. Fouling also occurred in the crystallizer. Recognizing these def... |
| Databáze: | OpenAIRE |
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