Wednesday, November 7, 2007
517c

Use Of A Continuous Countercurrent Centrifugal Extractor To Improve Cycle Time And Productivity Of Arzoxifene, A Novel Selective Estrogen Reuptake Modulator

Kevin D. Seibert1, Philip Hoffman2, Martin Johnson3, and Zheng Chen2. (1) Chermical Product Research and Development, Eli Lilly & Co., 1400 W. Raymond St., Indianapolis, IN 46221, (2) Chemical Product Research & Development, Eli Lilly & Co., Inc., 1400 W. Raymond St., Indianapoolis, IN 46221, (3) Chemical Process Research & Development, Eli Lilly &Co., Inc., 1400 W. Raymond St., Indianapolis, IN 46221

The synthesis of Arzoxifene, a novel selective estrogen reuptake modulator involves the removal of various residual solvents to improve reaction yield, conversion and selectivity. A series of batch-wise brine extractions were developed to afford both residual solvent removal and solvent transfer of the desired molecule. In an effort to improve cycle time and minimize a waste stream contaminated with a highly potent compound, a Robatel LX 126 continuous extractor was tested as a means of accomplishing the solvent switch and impurity removal. Results from modeling effort, neat solvent testing, and actual batch extraction trials indicate marked improvements in cycle time, impurity removal efficiency and reduction in total waste production.