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改进了沙格列汀中间体3-羟基-1-金刚烷甲基酮(1)的合成路线.以金刚烷甲酸(2)为起始原料,经二氯亚砜酰氯化后与N-氯代琥珀酰亚胺(NCS)反应制得3-氯-1-金刚烷甲酰氯(3);3依次经取代,脱羧和与碱反应合成1,其结构经1H NMR,IR和MS(ESI)确证.采用星点设计-效应面法对1合成条件进行了优化.结果表明:在最佳反应条件[228 mmol,n(NCS)/n(2)/n(AIBN)=1/0.83/0.65,于65 ℃反应8 h]下,1收率70%.“,”A route of synthesizing Saxagliptin intermediate,3-hydroxy-1-acetyladamantane(1) was im-proved.3-Chloro-1-adamantanecarbonyl chloride(3) was obtained by thionylchloride acylation from adamantanecarboxylic acid(2),and then reaction with N-Chlorosuccinimide(NCS).1 was synthesized by substitution,decarboxylation and alkalization from 3, respectivly.The structure was confirmed by 1 H NMR,IR and MS(ESI).Central composite design-response surface methodology was employed to optimize synthetic conditions of 1.The results demonstrated that under the optimum reaction conditions [2 28 mmol,n(NCS)/n(2)/n(AIBN)=1/0.83/0.65, reaction at 65 ℃ for 8 h], the yield of 1 was up to 70%.