Preparation method of 4-hydroxyl ketopyrrolidine-2-acetamide

Abstract

The invention provides a preparation method of 4-hydroxyl ketopyrrolidine-2-acetamide as a medicine with a cerebral metabolism improving function, comprising the following steps of: 1, reducing 4-halogenated acetylacetic ester as a raw material into 4-chloro-3hydroxybutyrate by using a reducing agent; and 2, condensing the obtained 4-chloro-3-hydroxybutyrate of the step 1 and glycine amide or glycine amide hydrochloride to obtain 4-hydroxyl ketopyrrolidine-2-acetamide and purifying the obtained 4-hydroxyl ketopyrrolidine-2-acetamide. The invention ensures that the total yield of a product is increased above 36 percent, shortens a process route and reaction time, reduces an intermediate process and is more suitable for the large-scale production of medical industry.

Description

technical field [0001] The invention belongs to the field of pharmaceutical fine chemicals, and in particular relates to a synthesis method of 4-hydroxypyrrolidone-2-acetamide. Background technique [0002] 4-Hydroxypyrrolidone-2-acetamide, commonly known as oxiracetam, is a drug for improving human brain metabolism. It has a central excitatory effect, can promote the vitality of semi-senescent cells, improve and promote the memory ability of the brain, can also resist hypoxia in the brain, and can improve brain function and metabolism. [0003] [0004] Oxiracetam molecular formula: C 6 h 10 N 2 o 3 Molecular weight: 158.16 [0005] 4-Hydroxypyrrolidone-2-acetamide was first developed by the Italian ISFS.P.A company and launched in 1987. So far, many companies have applied for patents on the synthesis process of 4-hydroxypyrrolidone-2-acetamide. According to the sequence of pyrrolidine ring formation, the synthetic routes can be divided into two categories: [00...

AI Technical Summary

Problems solved by technology

The problems in their production process are that there are many reaction steps, the total yield is low, and the "atom economy" is not high.

The "atom economy" of this type of process is relatively high, but the problem is that the total yield is low, and the final product has complex components, which can only be obtained after resin adsorption and desorption, and the purity cannot meet the requirements for medical use.

Requires low temperature and pressurized reaction, thus limiting its application in industrial production

[0012] In addition, in these inventions, organic bases, alkali metal or alkaline earth metal hydroxides such as potassium hydroxide, sodium hydroxide, calcium carbonate, or carbonates are generally used as acid-binding agents, and sodium carbonate is often used for economic considerations. , because it is a solid-liquid phase reaction, the reaction time is longer, generally 24-70 hours, and the reaction generates a large amount of solid salt, polluting the environment

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