To synthesis the important intermediates of saxagliptin and optimize its preparation process by the central composite design-response surface methodology. It was prepared from 1-adamantanecarboxylic acid by a mixture of sulfuric acid and nitric acid to obtain 3-hydroxy-1-adamantanecarboxylic acid,then was treated with acetyl chloride , sodium diethyl malonate and AcOH/H2O/H2SO4 to get 3-hydroxy-1-acetyladamantane.In this study, the central composite design-response surface methodology was employed to optimize the reaction temperature, reaction time and the mole ratio of 3-hydroxy-1-adamantanecarboxylic acid to acetyl chloride. The overall yield of 3-hydroxy-1-acetyladamantane based on 1-adamantanecarboxylic acid reached up to 70%. The optimized route shortened the reaction time ,saved cost and improved production efficiency,which was suitable for industrial production.