Preparation method of phenylephrine

Abstract

The invention discloses a preparation method of phenylephrine, which is characterized by comprising the following steps of: firstly adding alpha-benzyl methylamino m-hydroxy acetophenone hydrochloride to a solvent, and heating for dissolution; then adding a chiral catalyst at the temperature of 30-60 DEG C; introducing hydrogen after replacement of nitrogen; keeping relative pressure at 0.05+ / -0.01 MPa; carrying out catalytic hydrogenation for 10-20 hours, and then adding 18-25 percent by weight of ammonia water for reaction at the temperature of 15-25 DEG C, wherein the addition proportion of the ammonia water and the alpha-benzyl methylamino m-hydroxy acetophenone hydrochloride is 1.5:1-1:1; and separating and washing reaction products to obtain the phenylephrine. The invention has the advantages of simple production process, easy control of reaction conditions, few reaction byproducts, reduced environmental pollution, enhanced product yield coefficient, reduced production cost and product quality reaching the quality standard of the European pharmacopeia EP5.

Description

technical field [0001] The invention relates to the field of medicinal chemistry, in particular to a preparation method of phenylephrine. Background technique [0002] Phenylephrine is a pharmaceutical raw material intermediate with a wide range of applications. Its chemical name is (1R)-1-[3-hydroxyphenyl]-2-methylaminoethanol, and its molecular formula is: C 9 h 13 NO 2 , the main function is to strengthen myocardial contractility, constrict blood vessels, increase blood pressure, mainly used for medical emergency treatment of hypotension. At present, the annual demand for phenylephrine in the world is about 300 tons, and it is mainly sold to the United States, Japan, Southeast Asia, Europe, South America and other countries and regions. [0003] The current production process of phenylephrine is to obtain the final product through debenzylation, reduction, resolution and dissociation of α-benzylmethylamino-m-hydroxyacetophenone hydrochloride. The specific reaction is ...

AI Technical Summary

Problems solved by technology

[0006] 1. During debenzylation, high pressure reaction is required, the reaction conditions are harsh, and the product cost is high

[0007] 2. The end point of the reaction is not well controlled, resulting in incomplete reaction and difficult removal of subsequent impurities

[0008] 3. During debenzylation, some products are also reduced to form racemic hydrochloride, which is dissolved in water and is not easy to precipitate, resulting in low yield

[0009] 4. After the racemic base is obtained, it needs to be split. In theory, 50% of the product can be obtained. Although the remaining 50% can be racemized to obtain the racemic base, and then split to obtain the product, the steps are complicated and the yield is relatively high. Low

[0010] 5. There are many synthesis steps, and the mother liquor of each step is not easy to handle, resulting in great pollution to the environment when discharged

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