Butylphthalide synthesis method and purification technology

Abstract

The invention relates to a butylphthalide synthesis method. The method comprises the steps that methyl 2-formyl benzoic acid is adopted as a starting material, THF is adopted as a solvent to react with an n-butyl magnesium chloride Grignard reagent, and acid regulation is performed to prepare a butylphthalide product. The invention further relates to a technology for preparing high-purity butylphthalide. The obtained crude butylphthalide product is subjected to hydrolysis treatment by an alkaline substance, acid regulation is performed to separate out solids, and filtering is performed to obtain a butylphthalide midbody; the acid regulation and alkali regulation processes are executed repeatedly, and finally ring closure and decompression desolvation are performed to obtain high-purity butylphthalide. According to the synthesis method, low-flash diethyl ether is prevented from being adopted as a solvent, the purification technology is easy to implement, the reagent can be purchased in bulk easily, column chromatography product purification and reduced pressure distillation under high temperature and high vacuum degree are not needed, and industrial enlarged production is easy.

Description

technical field [0001] The invention relates to a new synthesis process for preparing high-purity anti-ischemic drug butylphthalide, which belongs to the field of medicine. Background technique [0002] Butylphthalide is the first national first-class new anti-ischemic drug with independent intellectual property rights and a new chemical structure after my country's accession to the WHO, and it is also the first in the world with "ischemic stroke treatment" as its main indication. Brand new chemicals. The compound was first discovered from the extract of southern water celery seed, and then synthesized artificially. Its chemical name is: 3-butyl-1(3H)-isobenzofuranone, and its English name is: 3-Butylphthalide. CAS: 6066-49-5, its chemical structure is as follows: [0003] [0004] At present, butylphthalide is mainly based on o-formylbenzoic acid as a starting material, and there are fewer preparation methods reported at present. Some existing preparation processes are ...

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Problems solved by technology

[0013] Although the methods for preparing butylphthalide described above can successfully synthesize butylphthalide, the reported processes are not suitable for industrial production

In these synthetic methods, because o-carboxybenzaldehyde is cheap as a starting material, and the Grignard reagent industrialized production is easy to operate, so this route has the most industrialized method production prospect, but this route obtains the pharmaceutical standard in how to refine butylphthalide In terms of raw materials, there are obvious defects that are not suitable for industrial scale-up production. Some adopt column chromatography for purification, and some use vacuum distillation under high temperature and high vacuum conditions.

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