Optimization of the Synthesis of 2-Adamantanecarboxylic Acid

To date, compounds having an adamantane moiety have found wide application in the pharmaceutical indus-try. Despite the fact that most biologically active adamantyl-bearing derivatives contain substituents in the first position of the adamantane molecule, some derivatives with substituents in the second position have also shown valuable pharmacological properties. While 1-adamantanecarboxylic acid is an inexpensive and commercially available reagent, its 2-substituted analogue is substantially less available, and therefore, the development and optimization of approaches to the synthesis of 2-adamantanecarboxylic acid are of great importance. In this work, a three-stage method for the synthesis of 2-adamantanecarboxylic acid has been optimized, based on the Corey- Chaykovsky reaction of 2-adamantanone with trimethylsulphoxonium iodide in the presence of potassium hy-droxide, followed by acid-catalyzed opening of the oxirane ring and oxidation of aldehyde 9 to the target carbox-ylic acid. The total yield of the target product is 70 %.