3-羟基-1-金刚烷甲基酮的合成及其工艺优化

Synthesis of 3-hydroxy-1-acetyladamantane and Its Optimization

摘要:

制备沙格列汀的关键中间体3-羟基-1-金刚烷甲基酮，并采用星点设计-效应面法优化其制备工艺。 以1-金刚烷甲酸为原料，经混酸（H2SO4/HNO3）氧化得3-羟基-1-金刚烷甲酸，与乙酰氯反应后再经丙二酸二乙酯钠取代，在酸性条件下脱羧得3-羟基-1-金刚烷甲基酮。 最后选用星点设计-效应面法对反应影响较大的几个关键因素进行工艺优化。 工艺优化后，以1-金刚烷甲酸为原料来计算总收率可达70%。优化过的路线缩短了反应时间，节约了成本，提高了生产效率，使整个合成路线更具有实际应用价值。

Abstract:

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.