Preparation method of isopropyl 2-(3-nitrobenzylidene)acetoacetate

A technology of isopropyl acetate and nitrobenzylidene, applied in the field of medicine, can solve problems such as increasing the cost of industrialized production, unsatisfactory yield, etc., achieves improved yield and purity, shortened reaction time, and cheap and easy-to-obtain raw materials Effect

Inactive Publication Date: 2012-06-13
QINGDAO HUANGHAI PHARM CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Cool the reaction solution to room temperature and place it overnight, and filter the obtained crystals as the product. The yield is not ideal, which indirectly increases the cost of industrial production

Method used

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  • Preparation method of isopropyl 2-(3-nitrobenzylidene)acetoacetate
  • Preparation method of isopropyl 2-(3-nitrobenzylidene)acetoacetate
  • Preparation method of isopropyl 2-(3-nitrobenzylidene)acetoacetate

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Effect test

Embodiment 1

[0025] The preparation method of 2-(3-nitrobenzylidene) isopropyl acetoacetate of the present invention comprises the following steps:

[0026] In the reaction bottle of 1000ml, add 151g (1mol) 3-nitrobenzaldehyde, 500ml isopropanol respectively, after stirring at room temperature, add 156g (1.1mol) isopropyl acetoacetate, then add 3g acetic acid, 6.6g piperidine, The reaction was stirred at 80°C and tracked with the liquid phase. After the reaction is completed, filter while it is hot (suction filtration), concentrate the filtrate in vacuum to 2 / 3-3 / 4 volume, then cool to below 0°C under stirring conditions to crystallize overnight. Filtrate with suction and wash the resulting solid with a small amount of isopropanol. Dry at 40-50°C (2 hours). After recrystallization with isopropanol, 267.9 g of the product was obtained, the yield was 91.4%, and mp: 92.5-94.8°C. Test results such as figure 1 Shown: After 4 hours, the reaction reaches the end point, and there is basically ...

Embodiment 2

[0030] According to the feeding amount and operating method of "Example 1", the experiments with reaction times of 2h, 4h, 5h, 6h, and 8h were done respectively, and all the other operations were the same. The results are as follows: at 2 hours, the yield was 65% (mp: 92.0~94.0℃); at 4 hours, the yield was 91.4% (mp: 93.0~94.8℃); at 5 hours, the yield was 91.0% (mp: 92.7~ 94.6℃); at 6 hours, the yield was 90.8% (mp: 92.5~94.9℃); at 8 hours, the yield was 90.5% (mp: 92.8~94.9℃). The results showed that: in the range of 2-4 h, the yield increased with time; at 4 h, the yield reached the highest; after 4 h, the yield basically remained unchanged.

Embodiment 3

[0032] With the charging amount and operation method of "Example 1" respectively with the molar ratio of acetic acid and piperidine mixture catalyst being 1:2, 1:1, 2:3, 2:1, experiments were done, and the yields of the reaction products were respectively as follows : 80.42% (mp: 92.7-94.9°C), 90.39% (mp: 92.9-94.8°C), 85.89% (mp: 93.1-94.8°C), 76.87% (mp: 92.8-95.1°C). The results show that: when using acetic acid and piperidine with a molar ratio of 1:1 as a catalyst, the reactant reacts most completely and the yield is also the highest; when using acetic acid and piperidine with a molar ratio higher or lower than 1:1 as a catalyst, The reactant reacts incompletely, so the yield is also low, and the fact also proves that there are many reactants in the reaction solution.

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Abstract

The invention provides a preparation method of isopropyl 2-(3-nitrobenzylidene)acetoacetate, which comprises the following steps: carrying out condensation reaction on 3-nitrobenzaldehyde and isopropyl acetoacetate as initial raw materials by using an organic solvent as a solvent in the presence of catalysts acetic acid and piperidine for 2-8 hours; after carrying out vacuum concentration on the filtrate at 80 DEG C to 2 / 3-3 / 4 by volume, cooling to -5-5 DEG C while stirring to crystallize over night; and filtering, and recrystallizing with isopropanol to finally obtain the isopropyl 2-(3-nitrobenzylidene)acetoacetate. The invention shortens the reaction time; the isopropanol, which has lower toxicity than methylbenzene and can enhance the product yield and purity, is utilized as the reaction solvent; the catalytic rate of the catalysts is very high, the reaction is quicker and more thorough, and thus, the catalysts can enhance the yield; the invention enhances the yield and saves the cost; and since the refinement method of column chromatography separation, the technique is easy to operate, has the advantage of cheap and accessible raw materials, and thus, is suitable for industrial production.

Description

technical field [0001] The invention belongs to the field of medicine, in particular to a preparation method of 2-(3-nitrobenzylidene) isopropyl acetoacetate. Background technique [0002] Azclnidipine (Azclnidipine) is a new type of dihydropyridine drug, which was jointly developed by Sankyo and Ube Industries in Japan. Calcium channel blockers for blood pressure are currently on the market in more than a dozen countries around the world. It is a promising antihypertensive drug, and its effect is more specific. It is widely used clinically to lower blood pressure in mild or moderate essential hypertension, renal disorder with hypertension, and severe hypertension. Very good market prospects. [0003] 2-(3-nitrobenzylidene) isopropyl acetoacetate is one of the key intermediates in the synthesis of azedipine. At present, there are many reports about the preparation method of 2-(3-nitrobenzylidene) isopropyl acetoacetate. Society, 1982. ) After dissolving m-nitrobenzaldehy...

Claims

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Application Information

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IPC IPC(8): C07C205/56C07C201/12C07C201/16
Inventor 鲁大东毕文慧黄清华李延顺任晓飞于华芝
Owner QINGDAO HUANGHAI PHARM CO LTD
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