(466a) A Continuous Flow Grignard At Scale

Authors: 
Nwosu, S. O., Eli Lilly and Company
Johnson, M., Eli Lilly and Company
Seibert, K. D., Eli Lilly
Kopach, M., Eli Lilly and Company
Braden, T. M., Eli Lilly and Company
Kerr, M. S., Eli Lilly and Company
Adler, J. J., D&M Continuous Solutions
Schafer, J. P., D&M Continuous Solutions



Grignard reactions are common to pharmaceutical, fine and specialty chemical industries. These reactions are typically very exothermic with large adiabatic temperature rises, and are often water sensitive. Maintaining an inert atmosphere condition thus becomes critical throughout production, storage and use in order to maximize safety and yield.  

To improve the overall safety and control of a Grignard reaction at production scale, a CSTR (Continuous Stirred Tank Reactor) was installed to improve inertion capability, and exotherm control, while maintaining cycle-time with a significantly reduced reactor size. This route of operation has the added advantage of minimizing excess magnesium needed, and allowing for magnesium run out at the end of the cycle, thus minimizing the overall excess magnesium metal that will need to be disposed of at the end of the process.

Results will be presented to demonstrate the technical challenges and successful scale-up of the Grignard step from the laboratory, through the pilot plant, and into full scale production.

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