3-羟基-1-金刚烷甲基酮的合成及其工艺优化

以1-金刚烷甲酸为起始原料,经混酸(H_2SO_4/HNO_3)氧化得到3-羟基-1-金刚烷甲酸,经酰化、取代、脱羧得3-羟基-1-金刚烷甲基酮。考察了催化剂种类与用量、反应温度、反应时间、乙酰氯与3-羟基-1-金刚烷甲酸物质的量之比对3-羟基-1-金刚烷甲基酮收率的影响,确定了较佳的反应条件为:以吡啶为催化剂,n(吡啶)∶n(3-羟基-1-金刚烷甲酸)=1.5∶1,n(乙酰氯)∶n(3-羟基-1-金刚烷甲酸)=3.5∶1,反应温度为35℃,反应时间为3 h,在该条件下反应总收率约为70%(以1-金刚烷甲酸为基准)。

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

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.