Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

A kind of preparation method of S-metoprolol succinate

A technology of succinic acid and tartaric acid, applied in the preparation of carboxylate, preparation of organic compounds, chemical instruments and methods, etc., can solve the problem of low ee value of products, and achieve the effects of low cost, low risk factor and low energy consumption

Active Publication Date: 2015-09-30
ANHUI NEW STAR PHARMA DEV
View PDF5 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0009] The Chinese patent application whose publication number is CN102295569A discloses a method for preparing (S)-metoprolol succinate, which involves pumping 4-hydroxyphenethyl methyl ether and (R)-epichlorohydrin into the reactor , during the reaction process, the external circulating water outlet system filled with water removal agent is used to circulate the water, and the prepared (S)-3-[4-(2-methoxyethyl)phenoxy]-1,2-epoxy Propane reacts with isopropylamine to obtain (S)-metoprolol, and (S)-metoprolol is mixed with succinic acid to obtain (S)-succinic acid metoprolol again, and the final yield is greater than 75%, but The ee value of the product is not high

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

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • A kind of preparation method of S-metoprolol succinate
  • A kind of preparation method of S-metoprolol succinate
  • A kind of preparation method of S-metoprolol succinate

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0049] (1) 3.7kg of p-methoxyethylphenol, 7.4kg of anhydrous potassium carbonate, dissolved with 7.4kg of DMF (N,N-dimethylformamide), heated and stirred to 35°C, and 2.7kg of (R) -Epichlorohydrin, after dripping and keeping warm for 55 hours, TLC (ethyl acetate:dichloromethane=3:20) showed that the reaction was complete and the raw materials disappeared, and the reaction solution was poured into 30L of water and stirred evenly. The dichloromethane was extracted completely, the dichloromethane layer was washed with water and saturated brine respectively, the organic phase was dried with anhydrous sodium sulfate, and the dichloromethane was concentrated at 40°C to obtain an etherified product, which was directly used for the next reaction.

[0050] (2) At 25°C, dissolve the etherification product obtained in step (1) with isopropyl ether (about 10 kg), drop it into 4.25 kg of isopropylamine, and keep it warm overnight, TLC (EA:DCM=3:20) shows After the reaction is completed, co...

Embodiment 2

[0056] Except that the dibenzoyl-D-tartaric acid in the resolution step (4) is replaced by an equimolar amount of p-methoxydibenzoyl-D-tartaric acid, step (5) obtains S-metoprolol oil 1.15 kg, the HPLC purity of S-metoprolol at this moment is 99.5%, and the ee value is 99.4%.

Embodiment 3

[0058] Except that the dichloromethane in the resolution step (4) is replaced by 12L, tetrahydrofuran is replaced by 20L, step (5) obtains S-metoprolol oily matter 1.31kg, and the HPLC purity of S-metoprolol is 99.0% , ee value is 93.6%.

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 succinic acid S-metoprolol. The preparation method of the succinic acid S-metoprolol comprises that methoxyl ethyl phenol is taken as an initial raw material, (R)-epoxy chloropropane is taken as a reaction agent, and etherification reaction and amination reaction are carried out, so that an S-metoprolol crude product is obtained; then the S-metoprolol crude product and succinic acid form salt, dissociation is carried out by virtue of alkali for obtaining oily metoprolol, dibenzoyl-D-tartaric acid is used for splitting, so that an S-metoprolol pure product is obtained, and the obtained S-metoprolol pure product and succinic acid form salt, so that the succinic acid S-metoprolol is obtained. The preparation method of the succinic acid S-metoprolol has the advantages that S-metoprolol is salified and then purified, then splitting is carried out, and purity and ee value of the succinic acid S-metoprolol product are increased, and quality requirement in the field of medicines can be met.

Description

technical field [0001] The invention belongs to the field of drug synthesis, and in particular relates to a preparation method of S-metoprolol succinate. Background technique [0002] Metoprolol is an aminopropanol drug and a selective β1 receptor blocker. It competes with adrenaline and noradrenaline, protects the heart at the position of the receptor, inhibits cardiac contractility, and prevents nerve Impulse and avoid excessive excitement, it is one of the commonly used medicines for treating hypertension, coronary heart disease, chronic heart failure and arrhythmia, and it also has a good curative effect on angina pectoris caused by hypoxia. [0003] S-Metoprolol succinate (Metoprolol succinate), the structure is shown in formula (Ⅰ), Chinese alias: S-1-isopropylamino-3-[p-(2-methoxyethyl)phenoxy] -2-Propanol succinate is a white or off-white crystalline powder. API for angina pectoris and hypertension treatment. S-metoprolol succinate sustained-release tablets have s...

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 Patents(China)
IPC IPC(8): C07C217/32C07C213/10C07C213/08C07C55/10C07C51/41
Inventor 李晓祥狄潘潘徐自奥赵永海刘海亮李德刚
Owner ANHUI NEW STAR PHARMA DEV
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

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

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com