摘要
盐酸罗匹尼罗(ropinirole hydrochloride)是用于治疗帕金森症的第二代多巴胺激动剂药物,在参考文献的基础上以β-苯乙醇为原料,经与多聚甲醛在浓盐酸条件下关环后用3%摩尔当量的ZnCl2催化酯化得到氯甲基化合物,然后用DMSO氧化成醛,亲核加成后关环得到苯并吲哚酮,Ranney Ni催化加氢还原,水解脱保护,酯化,最后与二正丙胺通过取代反应后酸化制得,总收率18.4%。最终产品经过熔点、MS和1H-NMR测定。经过优化后该工艺路线具有成本较低,原料易得,操作简单,易于工业化等优点。
Ropinirole hydrochloride is a potent non-ergot dopamine receptor agonist and is being currently developed for the symptomatic treatment of Parkinson＇s disease.An improved process for the preparation of Ropinirole hydrochloride was studied and was described as follows.Cyclizing of β-phenylethanol with polyformaldehyde at concentrated hydrochloric acid followed by esterification with benzoyl chloride catalyzed by 3% mole equivalent ZnCl2 affords 2-（chloromethyl）phenethyl benzoate.It was then oxidized by DMSO to get 2-formylphenethyl benzoate,and the intermediate was reacted with nitromethane in neutral,then cyclized with AcCl catalyzed by FeCl3 and reduced by H2 with Ranney Ni as catalyst to give 4-（2-hydroxyethyl）indolin-2-one.Finally it was esterificated with TsCl and substituted with di-n-propylamine to get the title compound with a total yield of 18.4%.Compared with the current technology,this described process has the merits of the lower cost,the easily obtained raw material and the easily production for industrial scale.The melting point of the title compound is the same as that reported in literature,and its structure was confirmed by MS and 1H-NMR.
出处
《高校化学工程学报》
EI
CAS
CSCD
北大核心
2010年第6期1011-1016,共6页
Journal of Chemical Engineering of Chinese Universities
