Challenges in Catalysis Applied to Pharmaceutical Development

2012 Spring Symposium

 
Alan M. Allgeier
DuPont (formerly Amgen Inc.)

Abstract – In the development of pharmaceuticals, catalysis plays a critical role and its practitioners must nimbly assimilate knowledge of organic chemistry, surface reactions, reaction engineering and product isolation. In this presentation we explore three themes in catalysis for the pharmaceutical industry: 1) Enabling New Reactivity, 2) Quality… Above All Else and 3) Speed to Decisions… Speed to Market.

New Reactivity: Asymmetric hydroformylation of norbornene and utilization of ketolactols as aldehyde surrogates in reductive amination are described as novel chemistries demonstrated on clinical manufacturing scale. In the latter case, density functional theory provides insight into the mechanism of the reaction.
Quality: The use of precious metal catalysts engenders challenges of removing potentially toxic metals to meet quality specifications. The emerging technique of HPLC with ICP/MS detection is a valuable tool for understanding the diversity of residual metal complexes and identifying process options to clear metal impurities. In one such development effort a unique dearomatization reaction was characterized and its mechanism elucidated.

Speed: In conducting hydrogenation catalysis for pharmaceuticals catalyst deactivation is inevitably observed at some stage of development. In one case deactivation was particularly dependent upon gas to liquid mass transfer rates in batch reactors. A method for measuring the volumetric mass transfer coefficient (kLa) is described. Using this information reduces risk associated with scale up from laboratory to manufacturing equipment.

Speaker’s Biography – Alan Allgeier grew up in the beautiful countryside of northwest Pennsylvania. He earned his Ph.D. in Inorganic Chemistry in 1997 from Northwestern University under the direction of Prof. Chad Mirkin. He completed post-doctoral studies in heterogeneous catalysis at DuPont under Dr. Theodore Koch and continued at DuPont working on hydrogenation processes for nylon monomers and specialty chemicals, as well as, homogeneously catalyzed olefin hydrocyanation for specialty chemical applications. In 2004 Dr. Allgeier moved to Amgen to establish a competency in heterogeneous catalysis and pressure chemistry in support of drug discovery and development. In 2011 he returned to DuPont to lead a laboratory in the Surface and Particle Science Competency. Through his career Dr. Allgeier has been a leader in professional organizations including Arrangements Chair, Program Chair, Treasurer and Chair of the Philadelphia Catalysis Club, Board member of the 19th North American Catalysis Society Meeting, and Chair of the Organic Reactions Catalysis Society and its 23rd Conference. He is a contributing author / inventor of sixteen journal articles and fourteen patents or patent applications and served as Guest Editor for Topics in Catalysis. His technical interests include catalytic reactions for hydrogenation, carbonylation, and coupling, as well as, catalyst deactivation and reactor design.