The History of Flow Chemistry at Eli Lilly and Company

Flow chemistry was initially used for speed to early-phase material delivery in the development labo-ratories, scaling-up chemical transformations that we would not or could not scale up batch for safety reasons. Some early examples included a Newman Kwart rearrangement, Claisen rearrangement, hydroformylation, and thermal imidazole cyclization. Next, flow chemistry was used to enable safe scale-up of hazardous chemistries to manufacturing plants. Examples included high-pressure hydrogenation, aerobic oxidation, and Grignard for-mation reactions. More recently, flow chemistry was used in Small Volume Continuous (SVC) processes, where highly potent oncolytic molecules were produced by fully continuous processes at about 10 kg/day including reaction, extraction, distillation, and crystallization, using disposable equipment contained in fume hoods.