Preparation of 2-(3-Hydroxy-1-Adamantyl)-2-Oxoacetic Acid: A Key Intermediate for Saxagliptin

An optimized synthetic approach to prepare 2-(3-hydroxy-1-adamantyl)-2-oxoacetic acid has been reported in a good yield under mild experimental conditions. It was synthesized from 1-adamantanecarboxylic acid via successful reaction with thionyl chloride and sodium diethyl malonate to give dimethyl (1-adamantylcarbonyl) malonate, which was subjected to hydrolysis and decarboxylation by a mixture of acetic acid with water and sulfuric acid and then oxidation by potassium permanganate. The synthesized adamantane derivative was utilized to saxagliptin.