(342g) Understanding of a Continuous Barbier-Type Grignard Process Via Mechanistic Modeling

Authors: 
Zhu, X., Amgen
Içten-Gençer, E., Amgen Inc
Beaver, M. G., Amgen Inc.
Robinson, J. A., Amgen Inc.
Allian, A., Amgen Inc.
Huggins, S., Amgen Inc.
Rolandi, P. A., Amgen Inc.
Walker, S., Amgen Inc
Hart, R. A., Amgen Inc
Xiong, S., Process Systems Enterprise
Goda, A., Process Systems Enterprise, Inc.
As part of the efforts to advance continuous manufacturing (CM) capabilities of small molecules at Amgen, an end-to-end mechanistic process model with in-depth understanding of each unit operation was developed to leverage in silico simulations to increase process understanding, improve process design, and synthesize control strategies. A heterogenous Barbier-type Grignard reaction was among the many unit operations characterized and modeled in the CM process.

Due to their heterogeneous nature and the hazards associated with processing highly exothermic mixtures, Grignard reactions can be challenging to operate at production scale. This presentation focuses on the development of a mechanistic model for this challenging class of reactions and the utilization of the developed model to investigate and identify operating conditions that satisfy process constraints for continuous manufacturing. Batch experiments were designed and executed to provide the kinetics data for estimating the kinetic parameters. The model was also compared with existing fit-for-purpose models in the literature.