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Prepn process of nifedipine

A technology of nifedipine and benzylidene compound, which is applied in the field of preparation of medicine nifedipine, can solve the problems of many by-products, cumbersome reaction process, low yield and the like, and achieves the effect of improving product quality

Inactive Publication Date: 2003-06-04
天津中安药业有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0010] 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

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0021] 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.

[0022] 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

[0023] 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.

[0024] 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

[0025] 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.

[0026] 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%.

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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] 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 determined by TLC method, and the reaction of o-nitrobenzaldehyde (IV) and ammonia produces a series of aldimines, such as: [0004] The generation of these aldimines not only reduces the yield of the main reaction, but also can generate a variety of by-products with complex str...

Claims

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Application Information

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Patent Type & Authority Applications(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
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