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

Prepn. process of nifedipine

A technology of nifedipine and o-nitrobenzaldehyde, applied in the direction of organic chemistry, can solve the problems of many by-products, low yield, cumbersome reaction process, etc., and achieve the effect of improving product quality

Inactive Publication Date: 2005-02-23
天津中安药业有限公司
View PDF2 Cites 9 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0013] The present invention provides a simple and effective synthetic method to solve the shortcomings of the known preparation method of nifedipine (I) such as low yield, many by-products, and cumbersome reaction process.

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
  • Prepn. process of nifedipine
  • Prepn. process of nifedipine
  • Prepn. process of nifedipine

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0026] Embodiment 1: in the flask that stirrer is equipped with, add the pyridine carboxylate of o-nitrobenzaldehyde 35g (0.23mol), methyl acetoacetate 28g (0.24mol), ethanol 56ml and catalytic amount, stir at 60 ℃ After reacting for 1 hour, a pale yellow benzylidene solution was obtained.

[0027] Add methyl acetoacetate and 21 ml of ammonia water to the above reaction solution, heat up and reflux for 7 hours, and filter to obtain 70 g of wet weight of crude nifedipine. Without drying the crude product, add 5 times the amount (V / W) of ethanol and 1g of activated carbon, heat and boil for 15 minutes, filter while hot, wash the carbon layer with 20ml of hot ethanol, cool the filtrate to 5°C, filter and wash the wet product at 60 Dry at ℃ to get 57g of nifedipine, mp172℃~173℃, yield 71.1%

Embodiment 2

[0028] Embodiment 2: in the flask that stirrer is equipped with, add the pyridine carboxylate of o-nitrobenzaldehyde 35g (0.23mol), methyl acetoacetate 28g (0.24mol), acetonitrile 35ml and catalytic amount, at 50 ℃ The reaction was stirred for 2 hours to obtain a pale yellow benzylidene solution.

[0029] Add methyl acetoacetate and 21ml of ammonia water to the above reaction solution, raise the temperature, react at 85°C for 5 hours, stir and cool down to 5°C, and filter to obtain 62g wet weight of crude nifedipine. Without drying the crude product, add 5 times the amount (V / W) of ethanol and 1g of activated carbon, heat and boil for 15 minutes, filter while hot, wash the carbon layer with 20ml of hot ethanol, cool the filtrate to 5°C, filter and wash the wet product at 60 After drying at ℃, 52.3g of nifedipine was obtained, mp 172℃~173℃, yield 65.2%.

Embodiment 3

[0030] Embodiment 3: in the flask that stirrer is equipped with, add the pyridine carboxylate of o-nitrobenzaldehyde 35g (0.23mol), methyl acetoacetate 28g (0.24mol), methyl alcohol 58ml and catalytic amount, stir at 50 ℃ After reacting for 2 hours, a pale yellow benzylidene solution was obtained.

[0031] Add methyl acetoacetate and 21 ml of ammonia water to the above reaction solution, heat up and reflux for 7 hours, stir and cool down to 5° C., and filter to obtain 70.5 g of wet weight of crude nifedipine. Without drying the crude product, add 5 times the amount (V / W) of ethanol and 1g of activated carbon, heat and boil for 15 minutes, filter while hot, wash the carbon layer with 20ml of hot ethanol, cool the filtrate to 5°C, filter and wash the wet product at 60 After drying at ℃, 57.1 g of nifedipine was obtained, mp 172℃~173℃, yield 71.2%.

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 present invention is preparation process of nifedipine and relates to the field of organic chemical technology. Under the action of pyridine carboxylate in the catalytic amount, o-nitrobenzaldehyde and methyl acetoacetate are made to react to produce intermediate benzylidene compound, which is reacted with methyl acetoacetate and ammonia directly to produce nifedipine. In o-nitrobenzaldehyde, the total yield of re-crystallized nifedipine may reach 70%.

Description

technical field [0001] The invention belongs to the technical field of organic chemistry, in particular to a preparation method of medicine nifedipine. Background technique [0002] There are many preparation methods of currently known cardiovascular drug nifedipine, and US3485847 (Bayer 1968) promptly synthesizes nifedipine from o-nitrobenzaldehyde (IV), methyl acetoacetate (III) and ammoniacal liquor in a solvent. Horizon (I): [0003] [0004] This synthesis method is simple and easy to operate, but the reaction yield is low and there are many by-products, and the impurity content in the crude product is about 7%. According to the literature, the product has at least 7 kinds of by-products measured by TLC, and the reaction of o-nitrobenzaldehyde (IV) and ammonia produces a series of aldimines, such as: [0005] [0006] The generation of these aldimines not only reduces the yield of the main reaction, but also can generate a variety of by-prod...

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): C07D211/90
Inventor 李世发倪钟贾立森房洪滨
Owner 天津中安药业有限公司
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