New process for preparing beta-arteether by single reaction kettle method by taking artemisinin as raw material

Abstract

The invention provides a method for semi-synthesizing beta-arteether by a single reaction kettle method by taking artemisinin as a raw material. In absolute ethyl alcohol or a moderate polarity ether solvent system such as tetrahydrofuran, borohydride such as potassium borohydride and the like is taken as a reducing agent to reduce artemisinin so as to obtain dihydroartemisinin. Without separation or purification, methanesulfonic acid, phosphoric acid or the like is added to adjust the pH value to neutral, and then, a catalyst such as Lewis acid ZnBr2 and the like is continuously added to react to prepare arteether. After reaction, separation and purification are directly carried out by way of extraction, crystallization and recrystallization to obtain beta-arteether with high yield (0.85k of beta-arteether is prepared from 1kg of artemisinin), wherein the content of beta-arteether is more than 99.0%; the content of the related substance alpha-arteether is less than 0.2%; the content of dihydroartemisinin is less than 0.1%; and the content of the total impurities is less than 0.5% of the quality product. The method has the advantages of simple process flow, low equipment requirement, convenience in operation, high atom economy, low carbon and environment friendliness, and is very suitable for industrial production.

Description

technical field [0001] The invention relates to a specific antimalarial drug-β-arteether derived from artemisinin, in particular to a new process for preparing arteether by using artemisinin as a raw material in a single reactor method. Background technique [0002] Artemisinin is a sesquiterpene lactone compound extracted and separated from the leaves of Artemisia annua (also known as Artemisia annua) by Chinese scientists in 1971. The most characteristic peroxygen bond in the structure of artemisinin is It is the key group for its pharmacodynamic activity. Artemisia annua (Artemisia annua) or its extracts have been used to treat malaria-related diseases for more than two thousand years. Compared with artemisinin, artemisinin series derivatives such as dihydroartemisinin, artemether, artemisinin Ethyl ether and artesunate have shown better antimalarial effects. Since 2000, they have replaced chloroquine, piperaquine, quinine, etc., and have become the preferred antimalaria...

AI Technical Summary

Problems solved by technology

[0008] (1) At present, artemisinin is used as a raw material, and the process of synthesizing artether after reduction to dihydroartemisinin is too low, and the highest yield is not more than 60% based on β-arteether;

[0009] (2) The reaction is incomplete, the raw materials remain, and the by-product α-arteether accounts for a large proportion, which affects the separation and purification of the final product of β-arteether, and it is difficult to control the key impurity α-arteether;

[0010] (3) Calculated from the starting point of artemisinin, there are relatively many technological processes, complex operations, and large investment in equipment;

[0011] (4) Low atomic economy, large amount of chemical raw materials used, many by-products and discharged waste, high energy consumption, and difficult process green control

[0012] Due to the above shortcomings, the production cost of β-arteether at home and abroad is high, and the product quality is difficult to control, so that the application of β-arteether has been very small. Compared with artemether and artesunate, it is less than 5% of the antimalarial market share

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