Method for recycling byproduct p-toluene magnesium sulfonate to synthesize tenofovir

Abstract

The invention relates to the technical field of medicine chemicals and in particular discloses a method for recycling a byproduct p-toluene magnesium sulfonate to synthesize tenofovir. According to the method, hydroxymethylphosphonic acid diethyl ester and paratoluensulfonyl chloride are adopted as raw materials, magnesium carbonate is adopted as an acid-binding agent, p-toluenesulfonyl oxymethyldiethyl phosphate is synthesized, tenofovir is synthesized from the p-toluenesulfonyl oxymethyl diethyl phosphate and R-9-(2-hydroxypropyl), and meanwhile, a byproduct p-toluene magnesium sulfonate isgenerated; and magnesium carbonate and sodium p-toluenesulfonate are generated through a reaction of the p-toluene magnesium sulfonate and sodium carbonate. According to the method, the byproduct p-toluene magnesium sulfonate is mainly recycled, process treatment difficulties are reduced, byproducts p-toluene magnesium sulfonate and magnesium chloride which are obtained after treatment are high in purity, export sales can be achieved, the magnesium carbonate can be applied to synthesis of the p-toluenesulfonyl oxymethyl diethyl phosphate, and the production cost can be reduced.

Description

technical field [0001] The invention relates to the technical field of medicinal chemistry, in particular to a method for synthesizing tenofovir by recycling magnesium p-toluenesulfonate as a by-product. Background technique [0002] Tenofovir disoproxil is a nucleotide antiviral drug developed and marketed by Gilead in the United States. In 2001, it was approved by the US FDA for the treatment of human immunodeficiency virus (HIV) infection. Due to its definite therapeutic effect, good applicability and appropriate dosage, it is the first-line anti-HIV drug recommended by multiple treatment guidelines. Tenofovir disoproxil and its compound preparations have become the largest sales of anti-AIDS drugs. In April and August 2008, based on the results of a large number of clinical trials, the European Union and the U.S. FDA approved it for the treatment of hepatitis B (hepatitis B), and was praised by experts as one of the best anti-hepatitis B drugs. expand further. Accord...

AI Technical Summary

Problems solved by technology

[0004] Tenofovir is the basis and key intermediate for the synthesis of tenofovir disoproxil, which is of great significance for the synthesis of tenofovir disoproxil. The existing synthesis of tenofovir uses adenine as the starting material. The by-product magnesium p-toluenesulfonate in the synthesis process is temporarily stored as a by-product without effective treatment and comprehensive utilization. Diethyl p-toluenesulfonyloxymethylphosphonate is a key intermediate for the synthesis of tenofovir. Most of the techniques are to use sodium carbonate, sodium bicarbonate or sodium hydroxide as acid-binding agent, and the separation of the by-product sodium p-toluenesulfonate and sodium chloride aqueous solution produced by the reaction is difficult, and the separated sodium p-toluenesulfonate and chlorine The sodium content is not high, it is difficult to achieve export, and it is not conducive to large-scale production and environmental protection

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