N-(6-氯-4-甲硫基-1-羰基异色烷-5-基)-三氟乙酰胺的合成

Synthesis of N-(6-chloro-4-methylthio-1-oxo-isochroman-5-yl)-trifluoroacetamide

对一种吲哚化合物的关键中间体———N-(6-氯-4-甲硫基-1-羰基异色烷-5-基)-三氟乙酰胺的合成进行了研究。以2-氯乙醇为原料,经甲硫醇钠的亲核取代和特戊酰氯的酯化反应,生成2-(甲硫基)乙基特戊酸酯,产率92.2%。以3-氨基-4-氯苯甲酸为原料,经酯化反应生成3-氨基-4-氯苯甲酸甲酯,产率80.0%。所得中间体2-(甲硫基)乙基特戊酸酯低温下经磺酰氯氧化,与中间体3-氨基-4-氯苯甲酸甲酯反应,所得产物经重排、水解和酰化反应得到目标化合物,总产率25.8%。

Synthesis of N-（ 6-chloro-4-methylthio-l-oxo-isochroman-5-yl ）-trifluoroacetamide, the key intermediate for an indole,was studied. Started from 2-chloroethanol,2-（methylthio） ethyl pivalate was obtained via neucleophilic substitution with sodium methanethiolate and esterification with pivaloyl chloride in overall yield of 92.2%. Treatment of 3-amino-4-chlorobenzoic acid with trimethoxymethane generated methyl 3-amino-4-chlorobenzoate in 80.0% yield. 2-（Methylthio） ethyl pivalate was oxidized by sulfuryl chloride, and then reacted with methyl 3-amino-4-chlorobenzoate followed by rearrangement.hvdrolvsis and acvlation to zive the title compound in overall vield of 25.8%.