Development of Suzuki–Miyaura Coupling between 4-Pyridine Boronate Derivatives and Aryl Halide to Suppress Phenylated Impurities Derived from Phosphorus Ligands

Abstract

A method has been developed to suppress the formation of impurities derived from the aryl group on the phosphorus atom of the ligand used in the Suzuki–Miyaura coupling of 4-pyridineboronic acid derivatives. 4-Arylpyridine, a key substructure in several active pharmaceutical ingredients (API), is typically synthesized using this coupling reaction. However, in API synthesis, the generation of impurities derived from the aryl group on the phosphorus atom of the ligand has posed a significant challenge. In previously reported Suzuki–Miyaura coupling of 4-pyridineboronic acid derivatives, both the desired product and the aforementioned impurities were obtained. Here, we present a method to address and resolve this problem.