卡巴拉汀中间体3-[(1-二甲氨基)乙基]苯酚的合成

Synthesis of intermediate of rivastigmine:3-(1-dimethylaminoethyl)phenol

以间羟基苯乙酮为原料,硼氢化钠还原,与甲胺在醇溶液中发生Borch还原胺化反应,制得3-[(1-甲氨基)乙基]苯酚;将40%的甲醛溶液滴入3-[(1-甲氨基)乙基]苯酚的甲醇溶液中,控温0~5℃,硼氢化钠还原,得到目标化合物3-[(1-二甲氨基)乙基]苯酚,其结构经^(1)H-NMR和LC/MS表征。产物纯度为99.3%,反应总收率63.1%(以间羟基苯乙酮计)。该制备工艺原料易得、反应步骤少、操作简便、收率较高,可用于工业化生产。

The target compound 3-(1-methylaminoethyl)phenol was synthesized through Borch reductive amination reaction between m-acetylphenol and methylamine with sodium borohydride as reducing agent in the alcohol solution.The intermediate of rivastigmine 3-(1-dimethylaminoethyl)phenol was prepared by using 40%formaldehyde solution and 3-(1-methylaminoethyl)phenol as the raw materials under 0~5℃with the reductant of sodium borohydride in the methanol solution.The structure of the final product was characterized by ^(1)H-NMR and LC/MS.The purity of the product was 99.3%,and the total yield was 63.1%(calculated based on macetylphenol).This preparation process was easy to obtain raw materials,less reaction steps,simple operation,high yield,and can be used in industrial production.