Large‐Scale Applications of Transition Metal Removal Techniques in the Manufacture of Pharmaceuticals

Transition metal removal technologies are commonplace in today's drug candidate manufacturing due to the preeminent role played by coupling reactions in route design. This chapter presents examples of metal scavenging techniques to remove palladium, copper, iron, iridium, nickel, rhodium, and ruthenium that have been demonstrated on large scale during the manufacture of pharmaceuticals through coupling reactions. The chapter emphasizes the workup procedure and conditions for metal removal. It explains extraction and adsorption methods that precipitate or capture or extract the metal while maintaining the coupling product in solution. The chapter describes methods that precipitate the coupling product while purging the metal to the filtrates. Many other technologies have been developed for the reduction of transition metal levels in intermediates and active pharmaceutical ingredients (APIs).