The document summarizes optimization work done on the oxime formation step in a multi-step process to produce a PPAR agonist drug. Initial issues with the step included high solids loading, long reaction time, and need for an extensive purification. Screening reaction conditions identified hydroxylamine free base and methanol as a solvent improved the reaction time and yield. Further, crystallizing the oxime product as a salt eliminated the need for an extractive workup, simplifying purification. The optimized process resulted in over 90% yield in under 18 hours with a clean crystalline product.
2. Oxime Formation The oxime formation is the second chemical transformation in a 5 step process designed to produce the pharmacologically active PPAR Agonist described in the publication: An Efficient Synthesis of a Duel PPAR /γ Agonist and the Formation of a Sterically Congested -Aryloxyisobutyric Acid via a Bargellini Reaction , Raymond J. Cvetovich, et al. , JOC 2005 , 70 (21), 8560. O H F 3 C N O H O H O H F 3 C O O H H 2 N O H
