Sequential Acetic Acid–Sodium Chloride Treatment to Control Salt Stoichiometry of a Hydrochloride Salt

The sequential treatment of an intermediate in the synthesis of GSK159797 with a protic acid and sodium chloride was developed to control the stoichiometry of the hydrochloric acid salt of the API. This offered significant advantages over addition of hydrochloric acid, thus avoiding decomposition of an acid-sensitive formamide group. A range of acids were investigated to determine the optimum pKa range in which to use the acid. The optimum process, using acetic acid, was performed on >100 kg input scale.