The preparation method of bilastine key intermediate

Abstract

The invention discloses a preparation method of a bilastine key intermediate 2-(4-ethoxy)-phenyl-2-methyl propionate. The method comprises the following steps: carrying out carbonyl reducing reaction on 2-(4-haloacetyl)-phenyl-2-methyl propionate under the action of a catalyst; carrying out cyclization in an alkaline solution; and then carrying out reduction reaction under the action of a catalyst, so as to obtain 2-(4-ethoxy)-phenyl-2-methyl propionate. According to the method disclosed by the invention, the severe condition in the prior art is avoided, and the method is available in raw materials, simple in operation, low in cost, friendly to environment and suitable for industrial production.

Description

technical field [0001] The invention belongs to the field of medicine preparation, in particular to a preparation method of 2-(4-hydroxyethyl)phenyl-2-methylpropionate. Background technique [0002] Bilastine, a second-generation histamine H developed for Spanish FAES company 1 Receptor antagonists, approved in the European Union in 2010, were one of 15 new molecular entities approved globally that year. As a second-generation antihistamine, bilastine is mainly used for the treatment of allergic rhinitis, urticaria and chronic asthma. Compared with the first-generation antihistamine, it has a lower central nervous system sedative effect, and is lethargic and weak after taking it. And other side effects are small. [0003] The Chinese chemical name of bilastine is: 2-[4-(2-(4-(1-(2-ethoxyethyl)-benzimidazol-2-yl)piperidin-1-yl)ethyl Base) phenyl] -2-methyl propionic acid, its structural formula is as follows: [0004] [0005] cas: 202189-78-4. [0006] WIPO Internati...

AI Technical Summary

Problems solved by technology

[0009] This reaction mainly has the following deficiencies: (1) raw material 1-methoxy group-1 (trimethylsilyloxy group)-2-methyl-1-propene and catalyst bis(dibenzylidene acetone) palladium and three tertiary The price of butyl phosphine etc. is all extremely expensive, is not easy to buy, and is difficult to preserve; (2) this reaction requires extremely strict anhydrous anaerobic conditions, and the operation is complicated, and the obtained product is difficult to purify; (3) remaining after the reaction is completed Both palladium and phosphorus will cause serious pollution to the environment

[0010] To sum up, this route has high cost, difficult operation, heavy pollution, and it is difficult to realize industrial production

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