150609-95-3Relevant articles and documents
Crystal form of 2,3:4,5-di-O-(1-methylethylidene)-beta-D-pyranofructose chlorosulfonate
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Paragraph 0068-0070; 0074-0076; 0079-0081; 0086-0088, (2020/01/25)
The invention belongs to the technical field of medicines and in particular relates to a crystal form I of 2,3:4,5-di-O-(1-methylethylidene)-beta-D-pyranofructose chlorosulfonate. The invention further relates to a preparation method and application of the crystal form in preparing topiramate. The crystal form I of the 2,3:4,5-di-O-(1-methylethylidene)-beta-D-pyranofructose chlorosulfonate, whichis provided by the invention, is high in purity, the content of a single impurity 2,3:4,5-di-O-(1-methylethylidene)-beta-D-pyranofructose is less than 0.15%, the yield of topiramate prepared from thecrystal form I of 2,3:4,5-di-O-(1-methylethylidene)-beta-D-pyranofructose chlorosulfonate is 92% or greater, the HPLC (high performance liquid chromatography) purity is greater than 99.85%, the content of the single impurity 2,3:4,5-di-O-(1-methylethylidene)-beta-D-pyranofructose is less than 0.06%, and the content of a single impurity of a condensation compound is smaller than 0.08%.
Preparation method of high-purity topiramate
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, (2018/09/08)
The invention discloses a preparation method of high-purity topiramate. The preparation method comprises the following steps: (1) performing reflux reaction on D-fructose and acetone in a dehydratingagent, centrifuging, then performing low-temperature reaction under a 4A molecular sieve-sulfuryl chloride-acid binding agent system, filtering and performing organic layer vacuum distillation; (2) dissolving a reaction product obtained in the step (1) by using a solvent, then introducing ammonia gas, stirring for 4-8 hours at a room temperature, vacuum-pumping for 0.5 h, increasing the temperature of reaction liquid, refluxing for 1 h, then slowly reducing the temperature to below 10 DEG C, crystallizing for 4 h, centrifuging and washing a filter cake with a solvent; (3) pressurizing a reaction product obtained in the step (2), increasing the temperature and dissolving, reducing the temperature to 65 DEG C, adding a small amount of topiramate seed crystals with a respective purity of morethan 99 percent, continuously reducing the temperature to 5 DEG C, crystallizing for 6 h, centrifuging and washing a filter cake with a low-temperature solvent to obtain the high-purity topiramate. The topiramate produced by the preparation method disclosed by the invention has the advantages of being abundant and cheap in raw material, low in cost, high in yield, high in purity, great in industrial value, low in pollution and the like.
Synthesis technology of topiramate
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Paragraph 0021-0023; 0026-0028; 0031-0033, (2017/08/27)
The invention provides a synthesis technology of topiramate and relates to the technical field of drug synthesis. The synthesis technology of the topiramate comprises the following steps that (1) diacetone fructose and sulfonyl chloride are esterified under the alkalescence environment to obtain chlorosulfonate ester; (2) the chlorosulfonate ester is aminated in a mixed solvent of tetrahydrofuran/dichloromethane, and a crude topiramate product is obtained; (3) refining is conducted: the crude topiramate product is subjected to recrystallization, and refined topiramate is obtained; the method for preparing the topiramate is safe and easy to operate, multistep recrystallization is avoided, the cost is reduced, the production technology is simplified, and the method is suitable for industrial large scale production.