Method for preparing high-purity tolperisone hydrochloride

A technology of tolapazone hydrochloride and preparation process, applied in the field of medical technology, can solve the problems of complicated operation and high cost, and achieve the effects of high yield, good quality and shortening reaction time

Active Publication Date: 2020-02-28
HARVEST PHARMA HUNAN CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Since the presence of impurities will have a great impact on the purity of the final product, it is necessary to remove impurities from the finished product before reproducing the refined salt, so the operation is complicated and the cost is high

Method used

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  • Method for preparing high-purity tolperisone hydrochloride
  • Method for preparing high-purity tolperisone hydrochloride
  • Method for preparing high-purity tolperisone hydrochloride

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0046] With reference to the European Pharmacopoeia method, HPLC is used to test tolperone hydrochloride;

[0047] Step (1): Add 99.6g of toluene and 86.5g of anhydrous aluminum trichloride to the 250ml reaction bottle in sequence, and cool down to below 0°C;

[0048] Step (2): Slowly add 50g of propionyl chloride dropwise, and control the internal temperature below 0°C, then raise the temperature to 30-40°C, and react for 3 hours;

[0049] Step (3): After the reaction, slowly pour the reaction solution into 500 g of ice-water mixture, and control the internal temperature to be less than or equal to 15°C to quench and separate the liquids, concentrate the toluene phase and spin dry to obtain high-purity p-methylpropiophenone;

[0050] Step (4): Add 70g of p-methylpropiophenone, 46g of piperidine hydrochloride, 18.4g of paraformaldehyde and 46g of isopropanol into a 1000ml three-necked reaction flask, stir, heat up to an internal temperature of 90-100°C, and react 5 Hour;

[...

Embodiment 2

[0054] Compared with Example 1, the only difference is that in step (2), when slowly dripping 50g propionyl chloride, the internal temperature is controlled at 0-10°C; the product purity and impurity control are similar to Example 1, but the mass ratio of Example 1 The difference of 1; Owing to raising the temperature of dripping propionyl chloride, cause Friedel-Crafts acylation reaction by-product to increase, thereby influence product quality.

Embodiment 3

[0056] Compared with Example 1, the only difference is that in step (6), when the temperature is lowered to 25-35° C., there is no heat preservation reaction for 2 hours, and the total yield of refined products is only 47%. The product purity and impurity control are similar to Example 1. But the yield is low; because the heat preservation reaction was not continued for 2 hours at 25-35° C., the yield was low, which affected the product yield.

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Abstract

The invention relates to the technical field of medical processes, in particular to a method for preparing high-purity tolperisone hydrochloride. According to the method disclosed by the invention, the addition amounts of methylbenzene, anhydrous aluminum trichloride and propionyl chloride, a reaction temperature and reaction time in a Friedel-Crafts acylation reaction are strictly controlled; andafter a Mannich reaction is finished, cooling to 20-30 DEG C is performed, and isopropanol and isopropyl ether are added are added for heat-preserved crystallization for 2 hours or longer; and the solid-liquid separation is conducted to obtain a crude tolperisone hydrochloride product. The method for preparing the high-purity tolperisone hydrochloride can reduce Friedel-Crafts acylation side reactions, improve product purity and product yield, is environmentally friendly, and is easy, convenient and safe to operate.

Description

technical field [0001] The invention relates to the technical field of pharmaceutical technology, in particular to a process for preparing high-purity tolperone hydrochloride. Background technique [0002] Tolperisone Hydrochloride, molecular formula C 16 h 24 ClNO; molecular weight: 281.83, structural formula: [0003] [0004] Tolperone hydrochloride is a central muscle relaxant, and its indications are for the treatment of ischemic vascular diseases, such as arteriosclerosis, endovascular disease, etc.; it is also suitable for sequelae of stroke, cerebral palsy, and peripheral nerve disorders of the spinal cord. It has a certain curative effect on symptoms such as headache, dizziness, insomnia, limb numbness, memory loss, tinnitus and other symptoms caused by various cerebrovascular diseases. In recent years, a lot of research has been done on the synthesis of tolperone hydrochloride at home and abroad, and many synthetic methods have been introduced. [0005] Docu...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D295/108
CPCC07D295/108
Inventor 袁金桥秦敏张海军刘虎
Owner HARVEST PHARMA HUNAN CO LTD
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