Flow Chemistry from Milligrams to Metric Tons
Conference Recording Jun 26, 2014
About the Speaker
Scott May is Senior Research Advisor in the Small Molecule Design and Development group at Eli Lilly and Company in Indianapolis. Scott received his B.S. degree in chemistry from Hope College in 1993 and his Ph.D. in organic chemistry in 1998 at Indiana University working in the laboratory of Paul Grieco. Since joining Lilly in 1998, Scott has worked on the synthetic design and process development of new drug candidates from pre-clinical to advanced clinical trial phases. Throughout his career at Lilly Scott has focused on the identification, development and implementation of new technologies to accelerate the drug commercialization process. Scott co-founded the process development catalysis laboratory and has more recently helped build and lead Lilly’s continuous processing initiative. Abstract
In this presentation, a continuous, high pressure, Iridium-catalyzed reductive amination will be described from early proof-of-concept (milligrams) to a large scale manufacturing (2MT) demonstration under cGMP conditions. In this chemistry, a well established batch process utilizing the bulky reducing agent sodium triacetoxyborohydride (STAB) was successfully replaced with a safer, greener and more economic Ir-catalyzed continuous process. Key drivers for moving from a previously established high yielding batch process to a continuous process will be discussed. The choice of catalyst, solvent, reagent choices, additives and reaction conditions were important parameters that influenced catalyst stability and the impurity profile. The challenges of translating batch conditions into a continuous pipes-in-series reactor at several reaction scales will also be highlighted. The implementation of on-line HPLC will be presented to demonstrate the impact of this and other PAT on the development and manufacturing phases. Finally the technical transfer to manufacturing, plant operation considerations and campaign highlights will be presented.