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Method for preparing 2-fluoro-4-bromo trifluoromethoxyphenyl

A technology of bromotrifluoromethoxybenzene and trifluoromethoxybenzene is applied in the field of preparation of 2-fluoro-4-bromotrifluoromethoxybenzene, and can solve the problems of poor selectivity of metal reagents or Grignard reagents, fluorine The chemical agent process and equipment are difficult to realize, and it is difficult to industrialize production, so as to achieve the effect of less by-products, low cost, and easy industrialization in the synthesis route.

Active Publication Date: 2009-06-10
SHANGHAI CHEMSPEC CORP
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Although this method overcomes the shortcoming of high reaction temperature and many by-products of the above-mentioned halogen-fluorine exchange reaction, because the more halogens are carried on the benzene ring, the selectivity of the metal reagent or Grignard reagent is poorer, and the used It is difficult to realize the fluorinating agent and its process and equipment, and it is difficult to industrialize production

Method used

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  • Method for preparing 2-fluoro-4-bromo trifluoromethoxyphenyl

Examples

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preparation example Construction

[0012] Specifically, the preparation method of 2-fluoro-4-bromotrifluoromethoxybenzene comprises the following steps:

[0013] (1) Nitrate and nitrate 4-aminotrifluoromethoxybenzene to obtain 2-nitro-4-amino-trifluoromethoxybenzene;

[0014] (2) The obtained 2-nitro-4-amino-trifluoromethoxybenzene is subjected to diazotization and Sandmeyer reaction to obtain 2-nitro-4-bromotrifluoromethoxybenzene;

[0015] (3) The obtained 2-nitro-4-bromotrifluoromethoxybenzene is subjected to reduction, diazotization and Schiemann reaction to obtain 2-fluoro-4-bromotrifluoromethoxybenzene.

[0016] The synthesis route of the above-mentioned preparation method can be represented by the following reaction formula, for example.

[0017]

[0018] In the above method, preferably, the nitration reaction in the step (1) is carried out at a temperature range of -30°C to 50°C, more preferably, the nitration reaction in the step (1) is carried out at a temperature of -10°C to within a temperature...

Embodiment 1

[0033] Preparation of 2-nitro-4-aminotrifluoromethoxybenzene

[0034] At an internal temperature of -10°C to 10°C, add concentrated H 2 SO 4 (96%; 360g; 3.5mol) 25ml (0.555mol) of 95% nitric acid, 4-aminotrifluoromethoxybenzene (99.4%; 88.5g; 0.5mol), the reaction is exothermic, and the system is light yellow after dropping Thick, keep the internal temperature at -10°C ~ -5°C and stir until the raw materials are basically reacted. Pour into 500g+100ml of ice water, stir and filter with suction to obtain 9.5g of dark brown solid with a content of 89%. The filter cake is washed with 100ml×2 water and dried to obtain 140g of light yellow wet solid, which is dried to obtain 94.5g , organic phase chromatographic analysis, content 97.7%. The boiling point is 200°C.

Embodiment 2

[0036] Preparation of 2-nitro-4-bromotrifluoromethoxybenzene

[0037] Raise the internal temperature to 50°C, add CuBr 15g, HBr (48%) 420g (2.4mol), water 85ml, 2-nitro-4-aminotrifluoromethoxybenzene (98%) 108.5 g (0.48mol), NaNO 2 solution (NaNO 2 50g; 0.72mol / 120ml water), the reaction is exothermic, and bubbles will come out immediately, the reaction is basically kept at 50-55°C, and the sample is taken after the drop is completed, and there is no raw material. The system is layered, and the organic phase is washed with 20ml of 25% concentrated ammonia water to make 100ml of dilute ammonia water, which is neutral, solvent, distilled (10mmHg, top temperature 115°C ~ 117°C), and 120g of product is distilled out, analyzed by organic phase chromatography, the content 88.9%. The yield was 77.7%.

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Abstract

The invention discloses a method for preparing 2-fluorine-4-bromine(tri-fluoromethoxy)benzene. The method comprises the following steps: 1, 4-amino(tri-fluoromethoxy)benzene is nitrified to form 2-nitro-4-amino-(tri-fluoromethoxy)benzene; 2, the 2-nitro-4-amino-(tri-fluoromethoxy)benzene is subjected to diazotization and Sandmeyer reaction to form 2-nitro-4- bromine(tri-fluoromethoxy)benzene; and 3, the 2-nitro-4- bromine(tri-fluoromethoxy)benzene is subjected to reduction, diazotization and Schiemann reaction to form 2-fluorine-4- bromine(tri-fluoromethoxy)benzene. The method has the advantages of less by products on the synthetic route, mild and easily controlled reaction conditions, low cost, easy realization of industrialization, high production capability, and products obtained by the method has high purity and stable quality, and completely meets use requirements of a medicine intermediate.

Description

technical field [0001] The invention relates to a preparation method of 2-fluoro-4-bromotrifluoromethoxybenzene. Background technique [0002] 2-Fluoro-4-bromotrifluoromethoxybenzene is a pharmaceutical intermediate developed in recent years. Replacing a hydrogen atom on an aromatic ring with a fluorine atom often has a strong and unexpected effect on the biological activity of the compound. In biologically active molecules, replacement of a hydrogen atom with a fluorine atom often results in a similar compound with increased or improved biological activity. [0003] In the prior art, fluorination can be carried out by direct fluorination with a fluorinating agent. However, direct fluorination requires special reagents and equipment, is expensive, and the technology is immature, so it is not suitable for industrial production. Fluorination can also be carried out in the form of nucleophilic substitution via halogen-fluorine exchange reactions. However, this reaction ofte...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07C43/225C07C41/01
Inventor 袁云龙陈莹敏彭光荣
Owner SHANGHAI CHEMSPEC CORP
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