2-氯-6,7-二氢-5H-环戊并[b]吡啶的合成

实验以环戊酮与苄胺为起始原料,经亲核加成、乙酰化、Vilsmeier反应关环合成了第四代抗生素头孢匹罗的重要中间体2-氯-6,7-二氢-5 H-环戊并b]吡啶,经3步反应制备了2-氯-6,7-二氢-5 H-环戊并b]吡啶。合成中间产物N-亚环戊基苄胺的较佳条件为:反应温度为117～121℃,n(苄胺)∶n(环戊酮)=1∶1.02,回流反应时间为40min;合成中间产物N-环戊烯基-N-苄基乙酰胺的较佳条件为:加料温度0～5℃,反应温度25℃,n(苄胺)∶n(乙酸酐)=1∶1.1,反应时间14h;合成2-氯-6,7-二氢-5 H-环戊并b]吡啶的条件为:三氯氧磷加料温度0～5℃,回流反应时间15h,水解温度为40～45℃。三步反应的总收率为45.9%,产品结构经1 H NMR和LC-MS确证。

SYNTHESIS OF 2-CHLORO-6,7-DIHYDRO-5H-CYCLOPENTANO[b]PYRIDINE

The important intermediate of the fourth-generation antibiotics cefpirome,2-chloro-6,7-dihydro-5H-cyclopentanob]pyridine,was synthesized from cyclopentanone and benzylamine via nucleophilic addition,acetylization and Vilsmeier cyclization.The main synthetic conditions were found.For the intermediate N-cyclopentylidene(phenyl) methanamine,the reaction temperature were 117-121 ℃ with material molar ratio n(benzylamine)∶n(cyclopentanone)=1∶1.02 and refluxing reaction time of 40 min.For the intermediate N-benzyl-N-cyclopentenylacetamide,the feed temperature was 0-5 ℃,reaction temperature 20-25 ℃,n(benzylamine) : n(acetic anhydride)=1∶1.1,reaction time 14 h.The optimal synthetic conditions for the product 2-chloro-6,7-dihydro-5H-cyclopentab]pyridine were detailed as follows: phosphorus oxychloride feed temperature 0-5 ℃,refluxing reaction time 15 h,hydrolysis temperature 40-45 ℃.The overall yield after the three-step reactions was 45.9% and the target product structure was confirmed by LC-MS and 1H NMR.