9-溴壬基-4’,4’,5’,5’,5’-五氟戊基硫醚的合成方法研究

Improved Synthesis of 1-bromo-9[(4,4,5,5,5-pentafluoropentyl)thio]-Nonane

9-溴壬基-4’,4’,5’,5’,5’-五氟戊基硫醚是合成氟维司群的重要中间体。为了进一步完善和优化氟维司群的合成工艺,本文以壬二醇为原料,经溴代和与硫脲反应后生成9-硫脲-1-壬醇;以4,4,5,5,5-五氟戊醇为原料,经磺酰化所得的磺酸酯与9-硫脲-1-壬醇在碱性条件下反应,生成9-(4’,4’,5’,5’,5’-五氟戊硫基)-1-壬醇,后再经溴代得目标产物9-溴壬基-4’,4’,5’,5’,5’-五氟戊基硫醚,总收率为54.6%。本文的研究结果表明:与文献方法相比,本文的合成方法操作简单、收率令人满意,有利于氟维司群的工业化生产。

1-bromo-9-[(4,4,5,5,5-pentafluoropentyl)thio]-Nonane is an important intermediate for the synthesis of Fulvestrant.In order to improve the synthesis of Fulvestrant,this thesis is dedicated to the discovery of a more reasonable synthesis route and the optimization of reaction conditions.9-bromononan-1ol(3) was obtained from nonane-1,9-diol(2) via hydrobromic acid,then it reacted with thiourea to generate the compound 2-(9-hydroxynonyl)-isothiouronium bromide(4).The sulfonylation of 4,4,5,5,5-Pentafluoropenta-nol(5) was synthesized by benzenesulfonyl chloride.A synthesis of the compound 9-(4,4,5,5,5-pentafluoropentylthio)nonan-1-ol(7) was carried out under base condition from starting materials of 4,4,5,5,5-pentafluoropentyl benzenesulfonate(6) and the compound 4,then the target product was given by bromonation of compound 7 in a yield of over 50%.Compared with conventional methods,this improved process explored the possibilities of optimizing synthesis route to accomplish a more industry-suitable route and the result is quite satisfying.This method is easily post treatments and is adaptable to plant-scale production.