The Art of Meeting Palladium Specifications in Active Pharmaceutical Ingredients Produced by Pd-Catalyzed Reactions

Abstract The use of palladium‐derived catalysts in the synthesis of fine chemicals, pharmaceutical intermediates and active pharmaceutical ingredients (APIs) has become quite common in the last few decades. The number of palladium‐catalyzed synthetic reactions (both achiral and chiral) available to chemists has provided access to more complex structures in fewer steps and with less waste, due to the catalytic nature of many of the methods. An unfortunate side effect of using palladium is the potential for palladium‐containing impurities to remain in the desired compound after isolation. This is an especially significant problem for the pharmaceutical industry since there is a low limit for heavy metal impurities allowed in the drug substance. Therefore, various methods of removing palladium impurities from organic compounds of pharmaceutical interest have been developed. This review will provide a survey of the published methods but is not meant to be inclusive of all published material in this area of research.