First- and Second-Generation Practical Syntheses of Chroman-4-one Derivative: A Key Intermediate for the Preparation of SERT/5-HT_1A Dual Inhibitors

Two approaches to large-scale synthesis of the key intermediate <b>9</b>, a precursor of novel dual inhibitors of SERT/5-HT_1A receptor, are described. These two approaches each feature a mild and efficient method for construction of the chroman-4-one scaffold, which can be used with substrates containing base-sensitive functionalities and enable synthesis on kilogram scale without chromatographic purification. The first-generation synthesis enables quick delivery of a kilogram quantity of the key intermediate <b>9</b> with only one slurry purification step. On the other hand, the highly practical second-generation synthesis is suitable for the multikilogram campaign