Development of a Grignard-Type Reaction for Manufacturing in a Continuous-Flow Reactor

• Fabrice G. J. Odille^†§
• Anna Stenemyr^†§
• Fritiof Pontén^*‡

• ^† Pharmaceutical Development R&D, Chemical Science, AstraZeneca, SE-151 85 Södertälje, Sweden
• ^‡ Innovative Medicines, Cardiovascular and Metabolic Diseases, Medicinal Chemistry, AstraZeneca R&D, Sweden
• ^§ SP Process Development, Forskargatan, Sweden

This paper describes the scale-up of a highly exothermic and fast reaction from a microreactor with an internal volume of less than 1 mL to a mesoreactor with an internal volume of 13.5 mL. The development of a continuous process for manufacturing a ketone from an ester using a Grignard reagent is described. The different steps undertaken and the considerations made to be able to operate in continuous mode and achieve a product output of ca. 0.5 kg are presented.

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