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Industrial preparation method of 2,4,5-trifluoro-3-methoxybenzoyl chloride

A technology of methoxybenzoyl chloride and methoxybenzoic acid, which is applied in the industrial preparation field of 2,4,5-trifluoro-3-methoxybenzoyl chloride, can solve the problem of high boiling point of aniline and ineffective substitution of fluorine. Complete, high cost and other problems, to avoid the loss of materials, control the reaction conversion rate, and avoid environmental pollution.

Active Publication Date: 2013-12-18
YUEYANG YETOP FINE CHEM
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Tetrafluorophthalic acid is originally a relatively expensive chemical raw material, and this route is not suitable for industrial production
The biggest problem with this method is that the price of aniline is high, and the cost of not recycling the raw materials is too high. If it is recycled, the boiling point of aniline is high, and the recycling will also require a higher cost. However, DMF is used as the solvent instead of fluorine, and the moisture in the system cannot be controlled to the ideal level. , the fluorine substitution is not complete, and the sum of disubstituted and trisubstituted products reaches about 15%, resulting in a final yield of less than 40%, which is not conducive to industrial production

Method used

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  • Industrial preparation method of 2,4,5-trifluoro-3-methoxybenzoyl chloride

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Embodiment 1

[0044] The preparation method of the 2,4,5-trifluoro-3-methoxybenzoyl chloride of the present embodiment comprises the following steps:

[0045] The first step: pump 1200kg of DMSO aqueous solution with a water content of 45-50% into a 2000L imidization kettle, add 300kg of tetrachlorophthalic anhydride, and add 85kg of monomethylamine aqueous solution (40% by weight) dropwise at a temperature below 35°C. Heat up to 105-110°C for reflux reaction for 10 hours, then cool down to 20-30°C for centrifugation, and dry the solid to obtain 310kg of N-methyltetrachlorophthalic imide. The mother liquor can be directly recycled;

[0046] Step 2: Pump 4000kg of anhydrous DMSO into a 5000L fluorination kettle, put in 900kg of anhydrous KF and 1000kg of N-methyltetrachlorophthalic imide, raise the temperature to 145-150°C for 2 hours, and then cool down to 70 °C, transfer to another kettle, add water to precipitate crystals, and centrifuge to obtain 950kg water-containing 20% ​​N-methyltetr...

Embodiment 2

[0053] The preparation method of the 2,4,5-trifluoro-3-methoxybenzoyl chloride of the present embodiment comprises the following steps:

[0054] The first step: 1300kg of DMF aqueous solution containing 45-50% water is pumped into the 2000L imidization kettle, 300kg of tetrachlorophthalic anhydride is put in, and 85kg of monomethylamine aqueous solution (40% by weight) is added dropwise at a temperature below 35°C. Heat up to 105-110°C for reflux reaction for 10 hours, then cool down to 20-30°C for centrifugation, and dry the solid to obtain 308kg of N-methyltetrachlorophthalic imide. The mother liquor can be directly recycled and reused;

[0055] The second step: pump 4000kg of anhydrous DMF into the 5000L fluorination kettle, put in 920kg of anhydrous KF and 1000kg of N-methyltetrachlorophthalic acid imide, raise the temperature to 145~150℃ for 2 hours, and then cool down to 70 ℃, transferred to another kettle, added water to precipitate crystals, and centrifuged to obtain 9...

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Abstract

The invention discloses an industrial preparation method of 2,4,5-trifluoro-3-methoxybenzoyl chloride. The industrial preparation method comprises the following steps: 1) using methylamine to react with tetrachlorophthalic anhydride to get N-methyl tetrachlorophthalimide; 2) enabling the N-methyl tetrachlorophthalimide obtained in the step 1) to react with an alkali metal fluoride to get N-methyl tetrafluorophthalimide; 3) enabling the N-methyl tetrafluorophthalimide obtained in the step 2) to perform mixed reaction with sodium hydroxide to get 2,4,5-trifluoro-3-hydroxy sodium phthalate and then performing decarboxylation and acidification to get 2,4,5-trifluoro-3-hydroxybenzoic acid; 4) enabling the 2,4,5-trifluoro-3-hydroxybenzoic acid obtained in the step 3) to react with dimethyl sulfate to get 2,4,5-trifluoro-3-methoxybenzoic acid sodium and then acidifying to get 2,4,5-trifluoro-3-methoxybenzoic acid; 5) enabling the 2,4,5-trifluoro-3-methoxybenzoic acid obtained in the step 4) to react with thionyl chloride and N,N-dimethylformamide to get the 2,4,5-trifluoro-3-methoxybenzoyl chloride.

Description

technical field [0001] The invention relates to a production process of a pharmaceutical intermediate, in particular to an industrial preparation method of 2,4,5-trifluoro-3-methoxybenzoyl chloride. Background technique [0002] 2,4,5-trifluoro-3-methoxybenzoyl chloride (as shown in formula I) is an important raw material for the synthesis of fluoroquinolone antibacterial drugs such as gatifloxacin, baloxacin, moxifloxacin, and Cannot be substituted by other substances. Among them, moxifloxacin is the only fluoroquinolone antibacterial drug that can compete with the eight major cephalosporins in terms of curative effect, and has few side effects and a very broad market prospect. [0003] [0004] The synthesis research of 2,4,5-trifluoro-3-methoxybenzoyl chloride has been continuously improved and improved in the past ten years. Although there are many synthetic routes, the valuable industrial production methods are all based on four Chlorophthalic anhydride was used as...

Claims

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Application Information

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IPC IPC(8): C07C65/21C07C51/60
Inventor 吴顶王志李中瑞兰彩虹周志军袁强强
Owner YUEYANG YETOP FINE CHEM
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