Synthesis method of sofosbuvir

Abstract

The invention provides a synthesis method of sofosbuvir. The synthesis method of the sofosbuvir comprises the following steps: performing mitsunobu reaction on ((2R,3R,4R)-3-benzoyloxy)-4-fluorine-5-hydroxyl-4-methyltetrahydrofuran-2-yl)methyl benzoate to produce sulfonate to obtain a compound 1; abutting the compound 1 and N-benzoylcytosine to produce a compound 2. The method adopts mitsunobu reaction to avoid production of an isomer, and the isomer is reduced to 5 percent or below; according to the method, sulfonate and N-benzoylcytosine are abutted, so the use ofa stannic chloride raw material is avoided; furthermore, the yield is high and few solid waste is generated during aftertreatment, so that the method is suitable for large-scale industrialized production.

Description

technical field [0001] The present invention relates to a synthetic method of sofosbuvir, in particular to a method of using Mitsunobu reaction to avoid the generation of isomers, which can reduce the isomers by less than 5%, and docking with N-benzoylcytosine with sulfonate , the synthetic method of sofosbuvir with high yield. Background technique [0002] In the original process, sulfuryl chloride was used to chlorinate hydroxy and then docked with N-benzoylcytosine under the action of tin tetrachloride to obtain the compound. [0003] In the original process, the ratio of chlorinated compounds to isomers is about 4:1, and about 20% of the isomers are in the reaction solution. [0004] The original research process uses tin tetrachloride with high activity in docking with N-benzoylcytosine, which is not easy for industrial production, and post-processing produces a large amount of solid waste. [0005] In the original research process, the compound reacted with ammonia-m...

AI Technical Summary

Problems solved by technology

[0004] The original research process is docked with N-benzoylcytosine and uses tin tetrachloride with high activity, which is not easy for industrial production, and post-processing produces a lot of solid waste

[0005] In the original research process, the compound reacted with ammonia-methanol solution to debenzoylate, but the reaction was slow, the reaction time was more than 24 hours, and the reaction was incomplete, and the yield was only 78%.

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