Preparation method of metformin hydrochloride

A technology of metformin hydrochloride and dimethylamine hydrochloride, which is applied in the field of preparation of metformin hydrochloride, can solve the problems of low solubility of metformin hydrochloride, potential safety hazards, flushing phenomenon, etc., and achieve mild conditions, high safety, and avoid flushing phenomenon Effect

Active Publication Date: 2013-12-11
QINGDAO HUANGHAI PHARM CO LTD
View PDF5 Cites 27 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] In addition, due to the low solubility of metformin hydrochloride in organic solvents, when the reaction reaches a certain level, metformin hydrochloride will be precipitated from the reaction solution in an instant, and the heat will be released violently.
Therefore, when using a solvent whose boiling point is close to the reaction temperature, it is easy to appear the flushing phenomenon, and there is a potential safety hazard

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0019] Add 200kg of N,N-dimethylacetamide (DMAc) into a 300L reaction tank, add 50kg of dicyandiamide and 50kg of dimethylamine hydrochloride under stirring, and heat to 140±5°C for 4 hours. After the reaction was completed, the temperature was lowered to 20-30°C for crystallization, and then dried by centrifugation. The filtrate recovers N,N-dimethylacetamide, which can be reused after passing the inspection. The obtained solid was dried under reduced pressure to obtain 83.3 kg of metformin hydrochloride crude product with a yield of 84.6% and a dicyandiamide content of 0.11%.

[0020] Refining: Add 250kg of 80% ethanol to a 500L reaction tank, add 83.3kg of the above-mentioned metformin hydrochloride crude product under stirring, and heat up to reflux. After the crude product is completely dissolved, adjust the pH value to 5~6 with hydrochloric acid. Then continue to reflux for 30min after adding 1kg of activated carbon. Pump the reaction liquid through an activated carbo...

Embodiment 2

[0022] Add 150kg of N,N-dimethylacetamide into a 300L reaction tank, add 50kg of dicyandiamide and 58kg of dimethylamine hydrochloride under stirring, heat to 140±5°C, and react for 6h. After the reaction was completed, the temperature was lowered to 20-30°C for crystallization, and then dried by centrifugation. The filtrate recovers N,N-dimethylacetamide, which can be reused after passing the inspection. The solid obtained by centrifugation was dried under reduced pressure to obtain 87.8 kg of metformin hydrochloride crude product. The yield is 89.1%, and the dicyandiamide content is 0.011%.

[0023] Refining is the same as in Example 1, and 79.3 kg of metformin hydrochloride is obtained, with a yield of 90.3%. Content 99.81%, dicyandiamide was not detected.

Embodiment 3

[0025] Add 100kg of N,N-dimethylacetamide into a 300L reaction tank, add 50kg of dicyandiamide and 50kg of dimethylamine hydrochloride under stirring conditions, heat to 140±5°C, and react for 6h. After the reaction was completed, the temperature was lowered to 20-30°C for crystallization, and then dried by centrifugation. N,N-dimethylacetamide was recovered from the filtrate. The solid obtained by centrifugation was dried under reduced pressure to obtain 91.0 kg of metformin hydrochloride crude product. The yield is 92.4%, and the dicyandiamide content is 0.021%.

[0026] Refining is the same as in Example 1, and 82.6 kg of metformin hydrochloride is obtained, with a yield of 90.8%. Content 99.70%, dicyandiamide content: 0.0026%.

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

No PUM Login to view more

Abstract

The invention discloses a preparation method of metformin hydrochloride. The preparation method is characterized by using dicyandiamide and dimethylamine hydrochloride as raw materials, feeding the materials in a mole ratio of (1:1)-(1:1.2), using N,N-dimethylacetamide or dimethyl sulfoxide 2-4 times dicyandiamide by weight as a solvent, and reacting for 4-8 hours at 140+/-5 DEG C to prepare a crude metformin hydrochloride product; recrystallizing the crude product with ethanol, regulating the pH value to be 5-6, decoloring the crystal, cooling the crystal to minus 10-0 DEG C while stirring, precipitating the crystal, obtaining a refined metformin hydrochloride product through filtering and drying, and recovering the solvent from filtrate. The qualified product has yield of 80-85% and high purity. The preparation method has the advantages that as the selected reaction solvent has a relatively high boiling point, the recovery rate of the solvent is high; the phenomenon of material surging can be effectively avoided, so that the preparation method has the advantages of mild reaction conditions, simplicity in operation and high safety.

Description

technical field [0001] The invention belongs to the field of medicine and chemical industry, and in particular relates to a preparation method of metformin hydrochloride. Background technique [0002] Metformin Hydrochloride is a biguanide antihypertensive drug. More than 50 years of clinical use have proved that Metformin has a good hypoglycemic effect and safety. [0003] Metformin hydrochloride can effectively control the weight of patients while lowering blood sugar, and reduce cardiovascular complications such as myocardial infarction in patients with type 2 diabetes. In addition, the price of metformin hydrochloride is low; it can be used in combination with sulfonylureas, glitazones and insulins; it is administered orally and is convenient and quick to take. [0004] At present, the synthetic methods of metformin hydrochloride mainly contain dry method and wet method. The dry method is the melting method, which is widely used. However, the initial and later stages...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Application Information

Patent Timeline
no application Login to view more
Patent Type & Authority Applications(China)
IPC IPC(8): C07C279/26C07C277/08
Inventor 黄清华刘晓华高永吉胡杰李延顺
Owner QINGDAO HUANGHAI PHARM CO LTD
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap