Preparation method of thioglycolic anhydride

Abstract

The invention discloses a preparation method of thioglycolic anhydride. The method comprises the following steps of: vaporization of trifluoroacetic anhydride: vaporizing trifluoroacetic anhydride ina vaporizing device for later use; synthesis of thioglycolic anhydride: preheating the interior of a suspended gas-solid reaction device to 45-65 DEG C, introducing the vaporized trifluoroacetic anhydride into the suspended-state gas-solid reaction device, intermittently adding thionyl diacetic acid from the top of the suspended-state gas-solid reaction device, reacting for 2 hours, stopping introducing the vaporized trifluoroacetic anhydride from a gas inlet, stopping heating, and leading out an obtained solid product from a discharging port; and purification of thioglycolic anhydride: washing the solid product with refrigerated anhydrous petroleum ether and anhydrous ether respectively to obtain pure thioglycolic anhydride. The thioglycolic anhydride synthesized by the method is high inpurity and high in yield; and the yield of erdosteine prepared by reacting the thioglycolic anhydride serving as a raw material with homocysteine thiolactone hydrochloride is high.

Description

technical field [0001] The present invention relates to the preparation of erdosteine ​​intermediate, in particular to a preparation method of thioglycolic anhydride. Background technique [0002] Erdosteine, chemical name: (±)-S-[2-[N-3-(2-oxotetrahydrothienyl)acetamido]]thioglycolic acid, is a kind of mucus-dissolving drug, used for acute Obstructive bronchitis, chronic obstructive bronchitis, bronchial asthma and other diseases cause sticky sputum and difficulty expectoration. [0003] At present, there are multiple synthetic methods as the key intermediate of synthetic erdosteine, thioglycolic anhydride, the most common method is the synthetic method of thiodiacetic acid and acid anhydride or acid chloride, such as: Chem.Pharm.Bull.50( 4) What is disclosed in the 558-562 (2002) article is to react by refluxing sulfidediacetic acid and acetic anhydride for 3 hours under the protection of nitrogen, and then vacuum concentrate after the reaction, and the concentrate is rec...

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Problems solved by technology

[0004] In summary, although the synthetic process of the key intermediate thioglycolic anhydride in the synthesis of erdosteine ​​is simple, there are problems of low reaction yield and long reaction time, and finally how to obtain high-quality, high-yield The problem of thioglycolic anhydride leads to the problem of low quality and low yield of subsequent synthesis of erdosteine

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