Continuous GMP Manufacturing for Grignard Reagent/Zincate Synthesis and Negishi Coupling Reaction

• Published in: Organic process research & development Vol. 28; no. 5; pp. 1734 - 1751
• Main Authors: Calvin, Joel R., Boyse, Raymond, Braden, Timothy M., Brewer, Alison C., Changi, Shujauddin, Harrold, Donal, Johnson, Martin, Kerr, Mark S., Lambertus, Gordon R., Luciani, Carla V., May, Scott A., Moloney, Harold, Murphy, John D., Roberts, Jeffrey C., Schafer, John P., Spencer, Richard D., Webster, Luke P.
• Format: Journal Article
• Language: English
• Published: American Chemical Society 17.05.2024
• Subjects: Grignard reagent; continuous manufacturing; GMP manufacturing; Negishi; zincate

A synthetic route to API was designed containing a Negishi cross-coupling reaction, where the zincate reagent was generated by transmetalation of a Grignard reagent. In order to manage the poor stability of the Grignard reagent, as well as safety concerns, the chemistry was developed as a flow proce...