MECHANISTIC STUDIES OF THE SUZUKI CROSS-COUPLING REACTION

The key step in the synthesis of the drug substance losartan is a pall adium-catalyzed cross-coupling reaction of an aryl bromide and a boron ic acid. The reaction scheme was defined in kinetic studies using HPLC , and computer simulation served to depict the time dependence of the concentrations of palladium species, which were not observed experimen tally. Two catalyst poisons were identified and characterized. One was an isomeric impurity of the aryl bromide; the other formed in the rea ction mixture upon hydrolysis of the boronic acid and two of its impur ities.