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

Preparation method of esomeprazole

A technology for esomeprazole sodium and omeprazole sodium, which is applied in the field of preparation of esomeprazole sodium, can solve the problems of high solvent toxicity, cumbersome operation, unsatisfactory purity and the like, and achieves controllable cost and easy operation. Simplicity, the effect of improving chemical and optical purity

Active Publication Date: 2014-03-26
CHENGDU YILUKANG MEDICAL TECH & SERVICE
View PDF3 Cites 4 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] The main purpose of the present invention is to provide a kind of esomeprazole sodium for the problems of low product yield, unsatisfactory purity, high solvent toxicity and cumbersome operation unsuitable for pharmaceutical industrial scale production in the above-mentioned prior art. preparation method

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
  • Preparation method of esomeprazole
  • Preparation method of esomeprazole
  • Preparation method of esomeprazole

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0052] Embodiment 1 The present embodiment is the preparation embodiment of esomeprazole sodium

[0053] Step (1) preparation of intermediate 1

[0054] Add 150ml of absolute ethanol and 3.0g of sodium hydroxide into a 250ml three-necked flask, heat and stir at 25-30°C for 2 hours, and then add 20.0g of omeprazole. Add 4.1 g of disodium hydrogen phosphate, continue stirring for 1 hour, transfer the reaction solution into a 250 ml single-necked bottle, evaporate to dryness in a water bath at 35-40 °C under reduced pressure, add 200 ml of acetone to the residue, stir and analyze at 10-15 °C crystal. After filtration, the filter cake was dried under reduced pressure at 35-40°C to obtain intermediate 1 with a yield of 98%, a purity of 99.914%, and a pH value of 10.8. The molar ratio of disodium hydrogen phosphate to omeprazole is 1:2.

[0055] Step (2) preparation of intermediate 2

[0056] Intermediate 1 prepared in step (1) was added with 12 g of titanium isopropoxide and 8....

Embodiment 2

[0066] Embodiment 2 The present embodiment is the embodiment of preparing esomeprazole sodium

[0067] Step (1) preparation of intermediate 1

[0068] Add 150ml of absolute ethanol and 3.0g of sodium hydroxide into a 250ml three-necked flask, heat and stir at 25-30°C for 3 hours, and then add 20g of omeprazole. Add 8.2 g of disodium hydrogen phosphate, continue to stir for 1.5 hours, transfer the reaction solution into a 250 ml single-necked bottle, evaporate to dryness under reduced pressure in a water bath at 35 to 40 ° C, add 200 ml of acetone to the residue and stir at 10 to 15 ° C to analyze crystal. After filtration, the filter cake was dried under reduced pressure at 35-40°C to obtain Intermediate 1 with a yield of 97%, a purity of 99.89%, and a pH value of Intermediate 1 of 10.7. The molar ratio of disodium hydrogen phosphate to omeprazole is 1:1.

[0069] Step (2) preparation of intermediate 2

[0070] With embodiment 1.

[0071] Step (3): Preparation of Intermed...

Embodiment 3

[0079] Embodiment 3 The present embodiment is the embodiment of preparing esomeprazole sodium

[0080] Step (1) preparation of intermediate 1

[0081] With embodiment 1.

[0082] Step (2) preparation of intermediate 2

[0083] With embodiment 1.

[0084] Step (3): Preparation of Intermediate 3

[0085] With embodiment 1.

[0086] Step (4): Preparation of Intermediate 4

[0087] Add 3.5g of sodium hydroxide and 200ml of ethyl acetate to 324.2g of the intermediate obtained in step (3) and 200ml of purified water, stir for 2 hours, separate layers, acidify the alkaline aqueous layer, extract with ethyl acetate, dry, evaporate under reduced pressure The crude product of intermediate 4 esomeprazole was dried; the molar ratio of sodium hydroxide to intermediate 3 was 6:1; the yield of intermediate 4 was 97%, and the HPLC purity was 99.811%.

[0088] Step (5): Preparation of intermediate 5

[0089] With embodiment 1.

[0090] Step (6): Refining

[0091] Add ethanol and activ...

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

PropertyMeasurementUnit
purityaaaaaaaaaa
optical purityaaaaaaaaaa
Login to View More

Abstract

The invention relates to the field of medicinal chemistry, in particular to a preparation method of esomeprazole. The preparation method of esomeprazole comprises the steps as follows: omeprazole is taken as an original raw material and subjected to complexation, separation, hydrolysis, salifying and refining, so that a product meeting the medicinal standard is obtained. With the adoption of the preparation method, the yield and the purity of esomeprazole can be remarkably improved, further, the reaction steps are simple, the environment protection is realized, the cost is controllable, and accordingly, the preparation method is suitable for industrial mass production.

Description

technical field [0001] The invention belongs to the technical field of medicinal chemistry, in particular to a preparation method of esomeprazole sodium. Background technique [0002] Omeprazole (trade name Losec) is a new type of proton pump inhibitor anti-ulcer drug launched by Swedish Astra Pharmaceutical Company in 1988. Omeprazole is a 1:1 mixture of R-type and S-type optical isomers, and its S optical isomer is esomeprazole. Esomeprazole, chemical name: (S)-5-methoxy-2-{[(4-methoxy-3,5-dimethyl-2-pyridyl)methyl]sulfinyl }-1H-benzimidazole, the molecular formula is: C 17 h 18 N 3 NaO 3 S, molecular weight: 367.4. The structure of esomeprazole is as follows: [0003] [0004] Esomeprazole sodium is the sodium salt of esomeprazole. Esomeprazole sodium is the world's first isomer proton pump inhibitor (PPI), which reduces gastric acid secretion through a specific targeting mechanism and is a specific inhibitor of proton pumps in parietal cells. [0005] In the pr...

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): C07D401/12
CPCC07D401/12
Inventor 李文军陶长戈向玲彭超骆均勇
Owner CHENGDU YILUKANG MEDICAL TECH & SERVICE
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