Preparation method of etilefrine hydrochloride

Abstract

The invention discloses a preparation method of etilefrine hydrochloride, comprising the following steps of: (1) adding alpha-bromo-m-hydroxyacetophenone to a solvent, stirring and dissolving, and then adding N-ethylbenzylamine at the temperature of 10-20 DEG C; carrying out heat preservation reaction for 3-6 hours, and then adding a hydrochloric acid solution to regulate the pH value to 0.5-1.5,and cooling to 10 DEG C or below; separating and washing to obtain alpha-benzyl ethyl amino-m-hydroxyacetophenone hydrochloride; (2) adding the alpha-benzyl ethyl amino-m-hydroxyacetophenone hydrochloride to an alcohol solvent and heating until dissolution; adding a catalyst; replacing with nitrogen and then introducing hydrogen; carrying out catalytic hydrogenation reaction for 12-24 hours at the relative pressure of not greater than 0.05MPa and at the temperature of 30-40 DEG C; and then crystallizing, separating and washing to obtain the etilefrine hydrochloride. The invention has the advantages of few reaction byproducts, high product yield, low production cost and little environmental pollution.

Description

technical field [0001] The invention relates to the field of medicinal chemistry, in particular to a preparation method of etiforine hydrochloride. Background technique [0002] Etiforine hydrochloride, the chemical name is 2-ethylamino-1-[3-hydroxyphenyl]ethanol hydrochloride, and the molecular formula is C 10 h 15 NO 2 ·HCl is an intermediate of pharmaceutical raw materials with a wide range of applications. Its function is to strengthen myocardial contractility, constrict blood vessels, and increase blood pressure. It is mainly used for medical emergency treatment of hypotension. At present, the world's annual demand for etiforine hydrochloride is about 100 tons, mainly in Europe, Southeast Asia, South America and other countries and regions. This product is in great demand abroad and has high added value. [0003] The current synthesis process of etiformine hydrochloride is generally to obtain the final product through amination, reduction and salt formation of α-bro...

AI Technical Summary

Problems solved by technology

[0005] The problems existing in the current production process are: one, there are two hydrogen atoms in the ethylamine molecule, and two brominated by-products are often generated during amination, resulting in low product purity and low yield; Ethylamine, there will be hydrobromide and hydrochloride of ethylamine, which is not easy to remove, so it can only be reduced and dissociated to obtain etiformine base, and then salted with hydrochloric acid to obtain etiforine hydrochloride, not only The process is complicated, the process is long, and the reduction and discharge of free mother liquor also pollute the environment

[0006] Because the production raw materials of etiforine hydrochloride are relatively expensive, the production cost is high, and in addition to factors such as low yield and heavy pollution in the above-mentioned current production process, many foreign manufacturers have stopped production

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