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Preparation method of ranitidine hydrochloride

A technology of ranitidine hydrochloride and ranitidine base, applied in the field of preparation of ranitidine hydrochloride, can solve the problems of incomplete removal of NDMA, low NDMA, no NDMA content, etc.

Pending Publication Date: 2022-06-07
石家庄海力药业有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] Chinese patent CN108017601 discloses a method for refining ranitidine base, which uses a mixed solvent of ethers and alcohols to refine ranitidine base. This method improves the purity by removing organic impurities, and there is no record about NDMA content.
[0005] Chinese patent CN112028862A discloses a preparation method of ranitidine hydrochloride with low NDMA content, the yield of ranitidine is the highest up to 85.12%, and NDMA cannot be completely removed

Method used

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preparation example Construction

[0025] The present invention provides a method for preparing ranitidine hydrochloride, comprising the following steps:

[0026] The ranitidine crude product was dissolved in a water-alcohol-cyclohexane mixed solvent to give the crude product solution;

[0027] The crude solution and activated carbon are mixed for decolorization to give a decolorization solution;

[0028] The decolorization solution and the ranitidine alkali seed are mixed and the first crystallization is carried out, and then filtered, washed and dried in turn to obtain the ranitidine fine product;

[0029] The ranitidine fine product and ethanol hydrochloride were mixed for the reaction to give the reaction solution; The reaction solution and ranitidine hydrochloride seed were mixed for a second crystallization, and then filtered, washed and dried in turn to give ranitidine hydrochloride; The purity of the ranitidine hydrochloride is more than 99.9%, and the NDMA content is 0.

[0030]The present invention dissol...

Embodiment 1

[0042]The ranitidine crude product with a content of 100g of 98.8% (containing 20.5% wetness, NDMA content of 0.68ppm, color number Y-5) was put into a 180g mixed solvent, the mixed solvent consisted of ethanol 36g, pure water 135g, cyclohexane 9g, heated to 47 °C under nitrogen protection, completely dissolved, added 0.4g activated carbon insulation for 1h, 47 °C filtering, filtrate cooled to 13 °C at 1.2 °C / 5 min, added 0.03g content of 99.97%, Ranitidine alkali seed with color number Y-1 and no NDMA, cooled to 1 °C at a cooling rate of 1.2 °C / 5min, kept warm for 3h, filtered, filter cake washed with 80g ethanol, spray dried at 63 °C, 73.1 g ranitidine fine product (purity 99.96%, color number Y-1, NDMA content of 0.02ppm), The ranitidine fine product and 102.34g ethanol were mixed, heated to 23 °C, 29% ethanol hydrochloride was added, the pH was adjusted to 6.5, the temperature was reduced at 1.4 °C / 5min, 9 °C was added with 0.0366 content of 99.95%, the color number was Y-1, n...

Embodiment 2

[0044]The ranitidine crude product with a content of 98.6% (containing 18.7% wetness, 0.85ppm, color number Y-4) of 100g of ranitidine was put into a 200g mixed solvent, the mixed solvent consisted of ethanol 35.25g, pure water 152.75g, cyclohexane 12g, heated to 45 °C under nitrogen protection, added 0.5g activated carbon insulation for 1h, 45 °C filter, filtrate cooled to 11 °C at 1.5 °C / 5 min, Add 0.04g of 99.97% light transmittance of 93.3%, NDMA-free ranitidine seed, cooled to 0 °C at a cooling rate of 1.5 °C / 5min, insulation for 4h, filter, filter cake washed with 50g ethanol, spray dried at 62 °C, to give 75.2g of ranitidine alkali boutique (purity of 99.95%, color number Y-1, NDMA content of 0.03ppm), The ranitidine fine product and 97.76g ethanol were mixed, heated to 24 °C, 27.5% ethanol hydrochloride was added, the pH was adjusted to 6.6, and then cooled at 1.3 °C / 5 min, 8 °C was added with 0.0301 g content of 99.95%, color number Y-1, no NDMA ranitidine hydrochloride s...

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Abstract

The invention relates to the technical field of compound purification and synthesis, and provides a preparation method of ranitidine hydrochloride. According to the method, the ranitidine base crude product is adopted as a raw material, the ranitidine base crude product is purified through decoloration and first crystallization to obtain a ranitidine base refined product, then the ranitidine base refined product reacts with hydrochloric acid ethanol, high-purity ranitidine hydrochloride is obtained through second crystallization, the purity of the finally obtained ranitidine hydrochloride is 99.9% or above, the NDMA content is 0, the color is light, and the purity is high. And the yield of ranitidine hydrochloride reaches 96% or above. The method provided by the invention is simple to operate, low in cost and suitable for industrial production.

Description

Technical field [0001] The present invention relates to the field of compound purification and synthesis technology, in particular to a method for preparing ranitidine hydrochloride. Background [0002] Ranitidine hydrochloride is an H2-receptor antagonist, which has a significant inhibitory effect on gastric acid secretion caused by physiological and pentapeptide gastrin, etc., for alleviating stomach pain, heartburn (heartburn), acid return caused by excessive gastric acid, while benign gastric ulcer, duodenal ulcer, anastomotic ulcer, reflux esophagitis, Zhuo-Ai syndrome also has a good therapeutic effect, due to oral absorption rapid, small dosage, less frequency of administration, small side effects, low recurrence rate, easy to be accepted by patients, It is an essential drug for the treatment of digestive diseases in various hospitals, and has been listed as a national essential drug by the Ministry of Health of China. After the reaction of ranitidine and hydrochloric acid...

Claims

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Application Information

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IPC IPC(8): C07D307/52
CPCC07D307/52
Inventor 朱玉梅张云堂李文革季建强邢孟平王晓
Owner 石家庄海力药业有限公司
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