Synthesis method of vinpocetine

Abstract

The invention discloses a synthesis method of vinpocetine. The synthesis method comprises adding vincamine into a three-neck flask, adding toluene into the three-neck bottle, stirring the mixture in ice water bath, dropwise adding polyphosphoric acid, placing the mixture into oil bath after half an hour, installing a water separator and a condensation tube, pumping to be vacuum, replacingnitrogen for two times, and performing reaction for 8 hours at the temperature of 120 DEG C; drying solvent by distillation after reaction is finished, adding ethanol and water, simultaneously dropwise adding caustic soda solution, utilizing saturated potassium carbonate solution to regulate pH to be 12 when the pH is 9, separating out solid, filtering and performing vacuum drying to obtain apovincamine; and adding absolute ethyl alcohol into the three-neck bottle, stirring the mixture in the ice water bath for one hour, then adding caustic alcohol into the mixture, adding the apovincamine after half an hour's stirring, placing a reaction bottle in the oil bath, performing reaction for 12 hours at the temperature of 80 DEG C, then steaming out solvent, adding the solvent into hydrochloric acid, extracting the mixture through ethyl acetate, adjusting pH value of the water phase to 12, separating out solid, filtering and drying to obtain the vinpocetine. The synthesis method is few in reaction step, low in energy consumption and less in environment pollution, recrystallization is not needed, and the purity of the vinpocetine can reach 99.5%.

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

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