Preparation method of oxiracetam

Abstract

Belonging to the technical field of medicine, the invention in particular relates to a preparation method of oxiracetam or pharmaceutically acceptable solvates thereof. The method includes the steps of: reacting oxiracetam acid with a compound R-CH2-OH to generate a compound with a structure shown as formula (I) in the specification, wherein R is defined as the specification. The invention also relates to the compound with a structure shown as formula (I) and application thereof in preparation of oxiracetam or pharmaceutically acceptable solvates thereof. The invention also relates to the use of R-CH2-OH in preparation of oxiracetam or pharmaceutically acceptable solvates thereof.

Description

technical field [0001] The invention belongs to the technical field of medicine, in particular to a method for preparing oxiracetam or a pharmaceutically acceptable solvate thereof. Background technique [0002] At present, my country's aging population is increasing, and Alzheimer's disease has a lot of impact on the lives of the patient himself, the patient's family, and the surrounding population, so it is increasingly concerned by the society. Oxiracetam is a nootropic drug used to improve memory and learning functions in patients with Alzheimer's and memory impairment. The drug was synthesized in 1974 and launched in 1984, and it is still widely used clinically. A large number of documents have reported the synthesis route and process of oxiracetam. The starting materials and reaction steps used in different processes are different, but in summary, there is the problem of low total yield. In some methods, because the intermediates need to be purified by column chroma...

AI Technical Summary

Problems solved by technology

However, the amount of water generated in this step is small, and water easily forms a uniform three-phase system with cyclohexane and ethanol, which cannot be separated, so the generated water cannot be removed, but still stays in the reaction solution

Although the esterification reaction time of the second step is as long as more than ten hours, the reaction cannot be advanced, so the reaction cannot be completely carried out

After the second step of the reaction, part of the oxiracetam acid still remains in the reaction mixture and cannot react with ammonia in the third step to form oxiracetam, which brings troubles to the subsequent purification and refining operation

Due to the many reaction sites, many by-products, and the reaction under strong alkaline conditions, the resulting oxiracetam is very unstable and easily decomposed, which in turn leads to complex composition of the reaction solution, which is difficult to purify and the reaction yield is not high and, due to the complexity of the reaction, gas by-products are generated, and the degree of gas removal is different, so that the composition and yield of the reaction product are also different, the reaction conditions are difficult to control, and it is difficult to form a stable process

Images