Use of Modeling and Process Analytical Technologies in the Design of a Catalytic Amination Reaction: Understanding Oxygen Sensitivity at the Lab and Manufacturing Scales

Autor:	Thomas M. Koenig, Hossam Moursy, Norma Scully, Utpal K. Singh, Neil J. Kallman, Jonas Y. Buser, Jeremy M. Merritt, Alison N. Campbell, Jared W. Fennell, Mark A. Pietz
Rok vydání:	2013
Předmět:	Active ingredient Process analytical technology Organic Chemistry chemistry.chemical_element Nanotechnology Oxygen Unit operation Catalysis Reaction rate chemistry Scientific method Biochemical engineering Physical and Theoretical Chemistry Amination
Zdroj:	Organic Process Research & Development. 18:246-256
ISSN:	1520-586X 1083-6160
Popis:	A mechanistic approach was undertaken to understand the oxygen sensitivity of a Pd-catalyzed amination reaction used in the synthesis of an active pharmaceutical ingredient. FlowNMR and dissolved oxygen probes were used as process analytical technology alongside kinetic and unit operation models to better characterize the oxidative deactivation pathways of the catalyst. Interplay between ligand excess, oxygen inertion, and additional degassing due to reflux were all found to contribute to reaction rate variability. This mechanistic approach allowed for appreciation and clear communication of the risks, development of protocols to mitigate those risks, and successful scale-up under rapid development timelines.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::95c46e60c18c6c78c1570fbe12aff961 https://doi.org/10.1021/op400226m Zobrazit plný text záznamu