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Scale-up of an Oxygen-Sensitive Miyaura Borylation
Christopher Mitchell of Takeda Pharmaceuticals discusses the scale-up of an oxygen-sensitive Miyaura borylation. A revised Miyaura borylation process was developed using tetrahydroxydiboron that avoids the use of bis(pinacolato) diboron and the need to hydrolyze the resulting boronic ester to its corresponding acid. The process was simplified and successfully scaled-up in the pilot plant on a 65 kg scale, reducing plant cycle time and resulting in a 47% overall cost reduction. Methodology for the study of the oxygen-sensitivity of the process is reported that allowed for optimization of the amount of tetrahydroxydiboron and catalyst used. These studies also demonstrated an oxygen-induced decomposition of tetrahydroxydiboron.
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The Scale-up of an Oxygen-Sensitive Miyaura Borylation presentation includes:
- Introduction and Overview of the Miyaura Borylation Step
- Review of the original conditions
- Use of bis-boronic acid
- Study of an Oxygen-Sensitive Process
- Equipment selection
- Experimental design and results
- Scale-up and Technical Transfer of the Process to Pilot Manufacturing
- Plant-scale experimentation and process design
- Review of the final manufacturing process
Boronic acids are important building blocks used extensively in a number of cross coupling reactions, including Suzuki-Miyayra and Chan-Lam, and are also of interest in medicinal chemistry. An estimated 25% of all reaction performed in the pharmaceutical industry are cross coupling reactions, mostly Suzuki couplings. Current state-of-the-art in synthesis of boronic acids includes transmetalation via metal/halogen exchange and Pd-catalyzed Miyaura borylation.
Who Should View the Scale-up of an Oxygen-Sensitive Miyaura Borylation On-Demand Webinar?
Scientists interested in process scale-up in the Pharmaceutical, Chemical, and Petrochemical Industries as well as Academia.
Presenter: Christopher Mitchell
Chris graduated from the University of Cambridge before starting his career as a Process Chemist at AstraZeneca. Following the closure of the Charnwood site, he joined Millennium Pharmaceuticals, now Takeda, in Cambridge, MA. At Takeda, his role evolved from a typical Process Chemist into a new role focusing on the engineering and chemistry aspects of scale-up from lab to plant. As part of this role, Chris has been involved with both the lab and the technical transfer to Contract Manufacturing Organizations. His activities center on the study of unit operations including the use of scale-down models and computational techniques. He also manages Takeda’s on-site kilo laboratory and has been involved in the design of a new highly potent development lab space at Takeda’s Boston site.