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研究了凡德他尼的关键中间体4-(N-Boc-4-哌啶甲氧基)-3-甲氧基苯甲酸甲酯的合成工艺。以4-哌啶甲酸乙酯为起始原料,将胺基用Boc酸酐保护起来,用LiAlH4还原得到N-Boc-4-哌啶甲醇,再与对甲苯磺酰氯进行反应,最后与香草酸甲酯进行取代反应制得目标化合物。对多种工艺条件进行优化,确定了最佳合成工艺,产率高达70.6%。产品经熔点测试,所得数据均与文献值吻合,结构经1HNMR进行表征。
The synthesis of methyl 4- (N-Boc-4-piperidinylmethoxy) -3-methoxybenzoate, a key intermediate of vandetanib, was studied. Starting from ethyl 4-piperidinecarboxylate, the amine group was protected with Boc anhydride and reduced with LiAlH4 to give N-Boc-4-piperidinemethanol, which was then reacted with p-toluenesulfonyl chloride and finally reacted with vanillic acid A Ester substitution reaction to obtain the target compound. A variety of process conditions were optimized to determine the best synthesis process, the yield was as high as 70.6%. Melting point of the product tested, the data obtained are consistent with the literature value, the structure was characterized by 1HNMR.