Preparation of ropinirole hydrochloride

Abstract

The invention relates to a method for preparing ropinirole hydrochloride, comprising the followings in turn: (1) beta-phenylethyl alcohol reacts with paraformaldehyde to produce isochroman; (2) the product obtained in step (1) reacts with bromide to produce 2-bromoethyl benzaldehyde; (3) the product obtained in step (2) reacts with nitromethane to produce 2-bromoethyl nitrostyrolene; (4) the product obtained in step (3) reacts with acetyl chloride to produce 4-bromoethyl-3-chloride-1, 3-dihydro-2H-indole-2-ketone; (5) 4-bromoethyl-1, 3- dihydro-2H-indole-2-ketone is obtained after catalytic hydrogenation of the product obtained in step (4); (6) 4-ethoxyl-1, 3-dihydro-2H-indole-2-ketone is obtained after acetylation and hydrolysis of the product obtained in step (5); (7) the product obtained in step (6) reacts with toluene sulfonic acid to produce toluene sulfonic acid-2-(2-oxygen-1, 3-dihydro-4-indole) ethyl ester; (8) the product obtained in step (7) and di-n-propylamine undergo reflux reaction in water and pH value is regulated by hydrochloric acid to 1-2 to obtain the ropinirole hydrochloride. In the method, the raw materials are easily acquired; the target products enjoy high selectivity and yield, thus being suitable for industrial production.

Description

technical field [0001] The present invention relates to a preparation method of ropinirole hydrochloride. Background technique [0002] Ropinirole hydrochloride, the chemical name is 4-[2-di-n-propylaminoethyl]-1,3-dihydro-2H-indol-2-one hydrochloride, is a U.S. GSK pharmaceutical company The company develops early-stage Parkinson's disease (PD) treatments. [0003] In the prior art, ropinirole hydrochloride is mainly synthesized with 5 kinds of different starting materials through 7 kinds of different process routes, which are respectively as follows: [0004] Route 1: [0005] [0006] Route 2: [0007] [0008] Route 3: [0009] [0010] Route 4: [0011] [0012] Route 5: [0013] [0014] Route 6: [0015] [0016] Route 7: [0017] [0018] In the above-mentioned route, route 1 is longer, and the starting material is expensive, and borane, cuprous chloride and potassium ethoxide are used in this route simultaneously, and it is necessary to ...

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Problems solved by technology

[0018] Among the above-mentioned routes, route 1 is relatively long and the starting materials are expensive. At the same time, borane, cuprous chloride and potassium ethylate are used in this route, which needs to be operated under anhydrous conditions, which increases the difficulty of production. At the same time, it also uses drastic Poisonous potassium cyanide; although the route 2 steps are short, special reagents and raw materials are used in the synthesis, which has little practical value; the raw materials of route 3 are simple and easy to get, but the reaction yield is low, especially in the substitution reaction of the last step The proportion of by-products in the medium is as high as 40%, which is not suitable for industrialized production; the route 4 is relatively long, and the first few steps of the reaction need to be operated under anhydrous conditions, which increases the difficulty of production; the starting material of the route 5 is expensive and the production cost is high; the reaction route 6 Harsh conditions, not suitable for industrialized production; route 7 starting materials are not easy to buy

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