A kind of preparation method of dihydropyridine crude drug

Abstract

The invention relates to a preparation method of a dihydropyridine raw material drug, comprising the following steps: putting ethyl acetoacetate and urotropine into a reaction kettle, mixing them at 15-20°C; slowly adding ethanolamine dropwise, and raising the temperature after the dropwise addition Reaction: cool down to crystallize, centrifuge to obtain crude dihydropyridine; add ethanol and crude dihydropyridine to the refining kettle, heat and stir to dissolve, adjust pH to neutral with glacial acetic acid, add activated carbon, stir for 1 hour, and then press into Crystallization kettle; crystallization at lower temperature, centrifugation, and vacuum drying to obtain dihydropyridine raw material medicine. The reaction process of the invention does not use organic solvents, has simple operation, less environmental pollution, mild reaction conditions, high safety, low cost, good product quality and is beneficial to industrialization.

Description

technical field [0001] The invention belongs to the field of synthesis and preparation of pharmaceutical raw materials, and in particular relates to a preparation method of dihydropyridine raw materials. Background technique [0002] The chemical name of diludine is 2,6-dimethyl-3,5-diethylcarboxylate-l,4-dihydropyridine, which is the first veterinary drug growth-promoting additive approved by the Ministry of Agriculture for use in my country. It is now included in the 2017 edition of the "Quality Standards for Veterinary Drugs" issued by the Ministry of Agriculture. Dihydropyridine is a new multi-functional additive with certain functions of natural antioxidant VE, which can inhibit the peroxidation process of lipid compounds and form a liver protective layer; it can protect the oil, vitamin VA and carotene in the feed from being oxidized antioxidant effect. At the same time, it can also change the level of some hormones in the serum, promote the growth and development of ...

AI Technical Summary

Problems solved by technology

[0006] At present, there are many ways to synthesize dihydropyridine, mainly the following three kinds. The first ammonia, formaldehyde, and ethyl acetoacetate are used as raw materials, and ethanol is used as a solvent. After reacting for 2 to 3 hours, cooling and crystallization, washing with ethanol, yield It is 50%, and this method cost height, and yield is lower, is raw material with a large amount of smell and bigger formaldehyde and ammoniacal liquor of toxicity, and environmental pollution is serious; The second kind is with formaldehyde, ethyl acetoacetate is raw material, and diethylamine is Catalyst, water is the solvent, reacted for 40-50 hours, layered, dried, added ethanol, passed ammonia gas, left for 40 hours, recovered the ethanol to obtain the product, and the yield was 84%. This method seriously pollutes the environment and consumes a lot of man-hours. The post-processing operation is loaded down with trivial details, is difficult to form large-scale production; The third kind of urotropine, ethyl acetoacetate, glacial acetic acid, strong ammonia water are raw materials, and ethanol and water are solvents, and this method uses a large amount of ethanol and water as solvents , The energy consumption of solvent recovery by distillation is high, and concentrated ammonia water is also used in the production process, which has a strong smell, poor operating environment, easy to cause environmental pollution, and high catalyst cost, so it is not suitable for large-scale use in industry

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