Synthesis method of vinpocetine

Abstract

The invention discloses a synthesis method of vinpocetine, comprising the following steps: adding vincamine into a three-opening bottle, subsequently, adding methylbenzene, stirring and dropwise adding triethylamine and methylsufonyl chloride in an ice-water bath, slowly heating to room temperature after stirring for 2 h, then continuously stirring for 5 h; stopping reaction, drying solvent by distillation, adding ethanol and water, regulating pH to 12 with saturated potassium carbonate solution, separating out solids, filtering, and drying in vacuum to obtain vinpocetine intermediate; adding absolute ethyl alcohol into the three-opening bottle, stirring in ice-water bath for 1 h, then slowly adding sodium ethoxide, stirring for 0.5 h, then adding the vinpocetine intermediate, subsequently, putting a reaction bottle into an oil bath, setting temperature as 80 degrees centigrade, evaporating most of solvent after reacting for 12 h, then pouring solution into hydrochloric acid, extracting with ethyl acetate, regulating pH to 12 with water phase, separating out solids, filtering and drying to obtain the vinpocetine. According to the synthesis method provided by the invention, reaction steps are short; purity and yield of products are high; energy consumption is low; and environmental pollution is less.

Description

technical field [0001] The invention relates to a synthesis method, in particular to a synthesis method of vinpocetine. technical background [0002] Vinpocetine is a structurally modified derivative of the indole alkaloid vincamine extracted from Apocynaceae vinca, and is an excellent drug for cerebrovascular diseases. Vinpocetine can increase the deformability of red blood cells, improve blood fluidity and microcirculation, reduce blood viscosity and inhibit platelet aggregation, and can increase and improve the supply of oxygen to the brain, and can selectively increase the local blood flow of brain lesions and improve Brain metabolism. It has been widely used clinically in foreign countries for ischemic hypertensive encephalopathy, cerebral arteriosclerosis, cerebral ischemia, intermittent cerebral blood flow insufficiency, cerebral vasospasm, early cerebral endarteritis, cerebral embolism, cerebral thrombosis, vertigo , aphasia, the treatment of Meniere's syndrome and...

AI Technical Summary

Problems solved by technology

The Mondelo patent reports that Vinpocetine is synthesized by using vinblastine as a raw material, acetonitrile as a solvent, and 2-fluoro-1,3,5-trinitrobenzene as a catalyst. The yield of this method is high, but the catalyst is rare and difficult. Realize industrialization, and using acetonitrile as a solvent is very toxic and not environmentally friendly

Kuge et al. used vincamine as a raw material to obtain vincamine ethyl ester through Ti(OEt)4 catalyzed transesterification, and then catalyzed dehydration with methanesulfonic acid to obtain vinpocetine. This method provides ideas for the large-scale production of vinpocetine, but The total yield is not high

Images