A kind of synthetic method of zilpaterol hydrochloride

Abstract

The invention provides a method for synthesizing zilpaterol hydrochloride. The method comprises the following steps: (1) hydrogenating a compound (h) under the action of a nickel-based catalyst to obtain 6-aminobenzimidazolidone azepine-7-one (compound k); (2) carrying out an alkylation reaction on the 6-aminobenzimidazolidinone azepine-7-one and 2-bromopropane to obtain 6-isopropylaminobenzimidazolidoneazepine-7-one (compound m); and (3) reducing the 6-isopropylaminobenzimidazolidinoneazepine-7-one to obtain zilpaterol. The method has the advantages of no high pressure conditions, low cost, simplicity in operation, and suitableness for industrial large-scale production.

Description

technical field

[0001] The invention relates to the field of chemical synthesis, in particular to a method for synthesizing zilpaterol hydrochloride. Background technique

[0002] Zipaterol hydrochloride is a beta-adrenoceptor agonist. Most of the existing synthetic methods adopt the synthetic route of U.S. Patent US4585770A (1986):

[0003]

[0004] (1) taking o-phenylenediamine (a) as starting material and ethyl acetoacetate in xylene, and potassium hydroxide as catalyst to synthesize isopropenyl benzimidazolone (b);

[0005] (2) condensation reaction of isopropenyl benzimidazolone (b) and ethyl bromobutyrate to generate N-isopropenyl benzimidazolone-N'-ethyl butyrate (c);

[0006] (3) N-isopropenyl benzimidazolone-N'-butyric acid ethyl ester (c) is alkaline hydrolyzed to obtain N-isopropenyl benzimidazolone-N'-butyric acid (d);

[0007]

[0008] (4) N-isopropenylbenzimidazolone-N'-butyric acid (d) is removed through acidic hydrolysis to obtain N-butyric acid benz...

Images