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Low-cost preparation method of 4'-bromomethyl -2- cyanobiphenyl

A cyanobiphenyl and bromomethyl technology is applied in the field of preparation of low-cost 4'-bromomethyl-2-cyanobiphenyl, and can solve the problem of reducing the bromination reaction speed, slow reaction speed, unsafe operation, etc. problem, to achieve the effect of easy industrial production, mild reaction conditions and high reaction selectivity

Pending Publication Date: 2018-06-15
安徽太主科技发展有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, this method produces a large amount of by-product hydrogen bromide in the reaction process, which will inhibit the bromination reaction, reduce the bromination reaction speed, and even incomplete reaction, so it is not suitable for commercial production
[0004] CN101200455A discloses that sartan biphenyl reacts with a brominating agent under light conditions to obtain a product, but in the large-scale production process, light energy is difficult to introduce into the interior and bottom of the reactor, which is not suitable for industrial production
Use HBr / NaBrO3 and Br2 / NaBrO3 oxidative bromination systems respectively, among which HBr and Br2 are highly corrosive and highly toxic high-risk reagents, which are corrosive to equipment and unsafe during operation. The industrial application value of this method is not high
[0007] WO2011073703 uses NaBrO3 / NaHSO3 oxidative bromination system, the amount of NaBrO3 is three times that of the substrate, the amount is large, the cost is high, and it is not suitable for commercial production
[0008] In summary, the preparation of 4'-bromomethyl-2-cyanobiphenyl has slow reaction speed, low industrial application value, high production cost, corrosion to equipment, unsafe operation, high cost, and is not suitable for industrial production

Method used

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Effect test

Embodiment 1

[0025] The preparation method of a kind of low-cost 4'-bromomethyl-2-cyanobiphenyl of the present invention comprises the following steps:

[0026] Step 1: Add ethyl acetate, water and sartan biphenyl to the reaction flask in sequence, then add bromide, bromate or chlorate, stir evenly at room temperature, control the reaction temperature at 35-45°C, add hydrochloric acid solution dropwise , the dropping time is 6 hours, after dropping, control the temperature at 35-45°C to continue the reaction for 1 hour, and detect the end point of the reaction by TLC;

[0027] Step 2: After the reaction, the organic phase is separated, 5 / 8 weight of ethyl acetate is recovered under normal pressure, the mother liquor is cooled to 0° C. for crystallization, and the pure product of 4′-bromomethyl-2-cyanobiphenyl is obtained by suction filtration.

[0028] Further, the bromide salt is sodium bromide or potassium bromide or lithium bromide or magnesium bromide or calcium bromide.

[0029] Furt...

Embodiment 2

[0034] The preparation method of a kind of low-cost 4'-bromomethyl-2-cyanobiphenyl described in the present invention, add 800 g ethyl acetate, 600 g drinking water, 193 g sartan to 3 L reaction bottle successively Benzene (1 eq), then add 69 g sodium bromide (0.67 eq), 50 g sodium bromate (0.33 eq), stir well at room temperature, control the reaction temperature 35 ~ 45 ° C, drop 200 g hydrochloric acid solution (concentration 20% , 1.1 eq), the dropping time is about 6 hours, after the dropping is completed, the temperature is controlled at 35-45°C and the reaction is continued for 1 hour, and the end point of the reaction is detected by TLC. Separate the organic phase, recover about 500 g of ethyl acetate under normal pressure, cool the mother liquor to about 0°C to crystallize, and then suction filter to obtain 231 g of pure 4′-bromomethyl-2-cyanobiphenyl, with a yield of 85% .

[0035] A kind of preparation method of 4'-bromomethyl-2-cyanobiphenyl described in the presen...

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PUM

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Abstract

The invention relates to the technical field of medicinal and chemical industries and specifically discloses a low-cost preparation method of 4'-bromomethyl -2- cyanobiphenyl. The low-cost preparationmethod comprises the following steps: sequentially adding ethyl acetate, water and 2-cyano-4'-methylbiphenyl into a reaction bottle, then, adding bromide, bromate or chlorate, carrying out uniform stirring at room temperature, controlling a reaction temperature at 35-45 DEG C, dropwise adding a hydrochloric acid solution for 6h, and after finishing dropping, controlling the temperature at 35-45 DEG C to carry out a further reaction for 1h, and detecting a reaction endpoint by an TLC; and after the reaction is ended, separating out an organic phase, recovering ethyl acetate accounting for 5 / 8of the weight at normal pressure, cooling a mother solution to 0 DEG C to carry out crystallization, and carrying out suction filtration to obtain a pure product of 4'-bromomethyl -2- cyanobiphenyl. By using the low-cost preparation method, defects in the prior art are overcome, ethyl acetate not only can serve as an organic solvent, but also can serve as a solvent for recrystallization, and ethylacetate accounting for 5 / 8 of the weight can be recovered at normal pressure after the reaction is ended, so that the preparation cost is effectively reduced.

Description

technical field [0001] The invention relates to the technical field of medicine and chemical industry, in particular to a preparation method of low-cost 4'-bromomethyl-2-cyanobiphenyl. Background technique [0002] Sartan drugs are the first-line antihypertensive drugs, with a brand-new antihypertensive mechanism, stable antihypertensive, good curative effect, long duration of action, and good patient tolerance. Most of the sartan drugs need to be prepared through the intermediate 4'-bromomethyl-2-cyanobiphenyl. The currently disclosed synthetic methods are as follows: [0003] US5621134 describes the preparation of 4'-bromomethyl-2-cyanobiphenyl by cheap bromine in the presence of sartanbiphenyl in the presence of free radical initiating reagents. However, this method produces a large amount of by-product hydrogen bromide during the reaction process, which will inhibit the bromination reaction, reduce the bromination reaction speed, and even incomplete reaction, so it is ...

Claims

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Application Information

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IPC IPC(8): C07C253/30C07C255/50
CPCC07C253/30C07C255/50
Inventor 欧阳细妹
Owner 安徽太主科技发展有限公司
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