Potassium isopropyl xanthate (PIX): an ultra-efficient palladium scavenger

The increasing employment of palladium-catalyzed reactions in the synthesis of active pharmaceutical ingredients (APIs) has created a pressing need for ultra-efficient palladium removal of the resulting metal contaminants. This communication discusses the identification and development of Potassium Isopropyl Xanthate (PIX) as a simple, readily available and ultra-efficient palladium scavenger capable of removing residual palladium from the API to levels less than 1 ppm. In addition, the discovery of a synergistic effect of iodine, in combination with PIX and other palladium scavengers, to enhance palladium removal has further increased the efficiency of the palladium removal process. The PIX and I 2 system has been successfully applied to the ceftolozane sulfate 2nd generation manufacturing chemistry to reduce palladium in the API resulting from a late stage palladium-catalyzed coupling reaction to only 0.1 ppm.