The Study On Synthesis Of Ropinirole Hydrochloride

Ropinirole, {4-[2-(di-n-propylamina)amino]-1,3-dihydro-2H-indolin-2-onehydro-chloride, SK&F 101468-A} has been shown to he a potent non-ergot dopamine receptor agonist and is currently being developed for the symptomatic treatment of Parkinson's disease, which was developed by Smithkine Beecham Co. of England.This paper relates to an improved process for the preparation of Ropinirole hydro- chloride. β -phenylethanol is selected as the raw material, via cyclization with polyformaldehyde at concentrated hydrochloride, esterification with benzoyl chloride in ZnCl₂ as the catalyst, oxidation in the existence of DMSO to get Formylphenethyl benzoate, then reacted with nitromethane in neutral, cyclization with AcCl in FeCl₃as catalyst, reduction with Ranney Ni, hydrolysis in 30% NaOH, esterification with TsCl, substitute with di-n-propylaminet to get ropinirole.The process for preparation of Ropinirole is optimized and improved. The details of the improvements as follows: the catalyst ZnCl₂ in synthesis of chloromethyl--phenethyl benzoate is reduced to lower the pollution, DMSO is used instead of HMTA at the oxidation step, the proportion of AcCl and FeCl₃ is adjust to improve the yield, then cheaper Ranney Ni is used to instead of Pd/C in the hydrogrnation.The yield attached to 18.4% in this route. And the finally product was identified by ¹H-NMR, ¹³C-NMR, IR, MS.