A kind of preparation method of vinpocetine

Abstract

The invention provides a preparation method for vinpocetine. The method comprises the following steps: with vincamine as a raw material and triethyl formate as an esterification reagent, subjecting vincamine and triethyl formate to a one-step reaction under the action of Lewis acid so as to obtain a crude vinpocetine product; and then carrying out washing with alkali lye, decoloring in alcohol and recrystallization so as to prepare a refined vinpocetine product. Compared with the prior art, the preparation method provided by the invention has the advantages of short process flow, simple operation and suitability for industrial production, and the prepared refined vinpocetine product has yield of more than 89%, a melting point of 148 to 151 DEG C, HPLC of greater than 99%, a whitish color, good quality and low preparation cost.

Description

technical field [0001] The invention relates to a preparation method of vinpocetine. Background technique [0002] Vinpocetine is an ivory amine, its English name: Vinpocetine, chemical name: ethyl (13 as, l3bs)-13α-ethyl-2,3,5,6-13α,13b hexahydro-1H-indole [3,2,1-de]pyridine[3,2,1-ij][1,5]-naphthyridine-12-carboxylic acid, the structural formula is as follows: [0003] [0004] Vinpocetine is a cerebral vasodilator, which can inhibit the activity of phosphodiesterase, increase the effect of c-GMP, the messenger of vascular smooth muscle relaxation, and selectively increase cerebral blood flow. In addition, it can also inhibit platelet aggregation, reduce human blood viscosity, enhance Red blood cell deformability, improve blood flow and microcirculation, promote brain tissue uptake of glucose, increase brain oxygen consumption, improve brain metabolism. [0005] There are mainly three kinds of synthetic methods of existing vinpocetine: one is to extract from the plant ...

AI Technical Summary

Problems solved by technology

[0007] Chen Rongrong, Pu Hanlin and others also used this method to synthesize Vinpocetine in "Semi-synthetic Process of Vinpocetine" ("Journal of Jinan University (Natural Science and Medicine Edition)" 2012 Issue 01), but the results were not ideal

[0008] Chinese patent application 201210151559.5 discloses a synthetic method of vinpocetine, which uses methanesulfonyl chloride to carry out mesylation and dehydroxylation, and then uses sodium ethoxide to carry out transesterification in ethanol solution, but it is found that the methyl exchange is difficult, and the reaction The temperature is high, and the time requirement is very long, so the reaction cannot be completed

[0009] Chinese patent application 201210388713.0 discloses a semi-synthetic method of vinpocetine, which uses an acid as a solvent to carry out high-temperature dehydroxylation, and then performs transesterification to obtain vinpocetine. Compared with the aforementioned method, this method is significantly improved, but the operation process is still complicated. Need to go through the column, and there are still problems such as incomplete transesterification

[0014] It can be seen from the reaction mechanism that the reaction may go through two intermediate states of compound A and compound B. The reason for the low yield and complicated operation of the existing process should be that neither compound A nor compound B has become a product. Vinpocetine has become an impurity, and the formation of a large amount of impurities not only reduces the yield, but also increases the difficulty of purification, and the operation process is naturally complicated