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Bromfenac sodium preparation method

A technology of bromfenac sodium and bromfenac, which is applied in the preparation of organic compounds, chemical instruments and methods, cyanide reaction preparation and other directions, can solve the problems of high cost, high production cost, complicated process and the like, and achieves a short synthesis route. Effect

Active Publication Date: 2017-02-15
山东辰欣佛都药业股份有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0008] The cyclization reaction of this route needs to be carried out at -70°C, and highly toxic Raney nickel is used, which is costly and polluting, and is not suitable for industrial production
The starting material of patent CN 104177272 A is prepared through multi-step synthesis, the process is relatively complicated, the production cost is relatively high, and it is not suitable for industrial production

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0023] The synthetic route of bromfenac sodium:

[0024]

[0025] The specific synthetic method of bromfenac sodium is as follows:

[0026] 1) Preparation of 3-bromoindole: Dissolve indole (234.4g, 2.0mol) in 3.5LDMSO, then add NBS (356.0g, 2.0mol), stir at 25°C for 6h, add 6L of water, cool to 10 ℃, stirring and centrifuging, washing the filter cake with 1.5 kg of purified water, and blow drying at 50 ℃ to obtain 380.0 g of the target product 3-bromoindole, with a yield of 96.94%.

[0027] 2) Preparation of 2-indolinone: 3-bromoindole (380.0g, 1.94mol) was added in 9L2-methoxyethanol, then dissolved and refluxed after stirring, phosphoric acid was added in four batches (750ml , add 3h intervals each time, add 3L phosphoric acid in total), react for 12h, cool to room temperature, add 9L purified water, cool to 10°C, centrifuge, wash the filter cake with 1.5kg purified water, and blow dry at 50°C to obtain 2-indole Indolin ketone 245g, the yield is 94.81%.

[0028] 3) Pre...

Embodiment 2

[0032] The synthetic route of bromfenac sodium:

[0033]

[0034] The specific synthetic method of bromfenac sodium is as follows:

[0035] 1) Preparation of 3-bromoindole: Dissolve indole (234.4g, 2.0mol) in 3.5LDMSO, then add NBS (356.0g, 2.0mol), stir at 35°C for 6h, add 6L of water, cool to 15 ℃, stirring and centrifuging, washing the filter cake with 1.5kg of purified water, and blow drying at 50 ℃ to obtain 382.0 g of the target product 3-bromoindole, with a yield of 97.45%.

[0036]2) Preparation of 2-indolinone: 3-bromoindole (382.0g, 1.93mol) was added in 9L2-methoxyethanol, then dissolved and refluxed after stirring, phosphoric acid was added in four batches (750ml , add 3h intervals each time, add 3L phosphoric acid in total), react for 12h, cool to room temperature, add 9L purified water, cool to 15°C, centrifuge, wash the filter cake with 1.5kg purified water, blow dry at 50°C to obtain 2-indole Indolin 247g, the yield is 95.11%.

[0037] 3) Preparation of 7...

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PUM

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Abstract

The invention relates to a bromfenac sodium preparation method. The preparation method comprises specific steps as follows: indole reacts under the action of DMSO (dimethylsulfoxide) to produce 3-bromoindole; 3-bromoindole is added to 2-methoxyethanol, acid is added for hydrolysis, and 2-indolinone is obtained; boron trichloride is added to methylbenzene, a methylbenzene mixed solution of p-bromobenzonitrile and 2-indolinone is added dropwise, aluminum chloride is then added, acid is added, a reaction is performed, and 7-(4-bromobenzoyl)-1,3-dihydro-indol-2-one is obtained; hydrolysis is performed with an alkaline solution, acid is added for neutralization, and bromfenac is obtained; ethanol is added to bromfenac, bromfenac and a sodium hydroxide solution form salt, the salt is cooled and subjected to recrystallization, and bromfenac sodium is obtained. Compared with the prior art, the synthetic route is short, high-purity bromfenac sodium can be prepared, the quality meets the latest standards of pharmacopoeia, industrial production is facilitated, and the method can provide powerful guarantee for industrial production of bromfenac sodium and intermediates of bromfenac sodium.

Description

technical field [0001] The invention belongs to the technical field of medicine preparation, and in particular relates to a preparation method of bromfenac sodium. Background technique [0002] Bromfenac sodium is one of the derivatives of 2-amino-3-benzoylphenylacetic acid. Its chemical name is 2-amino-3-(4-bromobenzoyl)sodium phenylacetate. The English name is Bromfena sodium. It is a yellow or orange-yellow crystalline powder. It is a non-steroidal anti-inflammatory drug developed by Wyeth-Ayerst Company. It has a strong analgesic effect and was launched in the United States in 1997. It is used for the treatment of sharp pain and is non-addictive. It was subsequently developed by Japan's Chishou Company as eye drops and used for the symptomatic treatment of inflammatory diseases in the outer eye and anterior eye. It is the most effective epoxy and enzyme inhibitor. Bromfenac sodium has the following structure: [0003] [0004] At present, the preparation method of b...

Claims

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Application Information

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IPC IPC(8): C07C227/22C07C229/42
CPCC07C227/22C07D209/30C07D209/34C07C229/42
Inventor 张乐波孙守飞何作鹏司呈元张百坤
Owner 山东辰欣佛都药业股份有限公司
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