Method for preparing bromfenac sodium

A technology of bromfenac sodium and monohydric alcohol, which is applied in the field of medicine and chemical industry, can solve the problems of non-recyclable solvents and high environmental protection treatment costs, and achieve the effects of increased product yield, low disposal costs and saving production costs

Active Publication Date: 2019-04-12
HEFEI JIUNUO MEDICAL TECH
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0006] In summary, 7-(4-bromobenzoyl)-1,3-dihydro-2H-indol-2-one is used to prepare bromfenac sodium through sodium alkali hydrol...

Method used

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  • Method for preparing bromfenac sodium
  • Method for preparing bromfenac sodium
  • Method for preparing bromfenac sodium

Examples

Experimental program
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Effect test

Embodiment 1

[0033] 30L of 60% methanol, 2.5kg (62.5mol) of sodium hydroxide, and 10kg of 7-(4-bromobenzoyl)-1,3-dihydro-2H-indol-2-one were successively put into the pressurized reactor (31.6mol), reacted at 90°C for 5 hours, cooled to 20-30°C, added dropwise hydrochloric acid to adjust the pH to 11, added 500g of activated carbon, stirred and decolorized under normal pressure for 30min, filtered while hot, and cooled the filtrate to 15-20°C , add seed crystals and stand for crystallization for 2h, then stand for crystallization at 0-10°C for 2h, -10-0°C for 3h, filter, and dry the solid in vacuum at 40-50°C for 6h to obtain orange-yellow Bromophenolate sodium 10kg, yield 88.9%, purity 100% (HPLC method).

Embodiment 2

[0035] Into the pressurized reactor, 36L of 70% methanol, 1.9kg (47.5mol) of sodium hydroxide, and 10kg of 7-(4-bromobenzoyl)-1,3-dihydro-2H-indol-2-one were successively put into the pressurized reactor (31.6mol), reacted at 110°C for 3h under closed stirring, cooled to 20-30°C, added dropwise hydrochloric acid to adjust the pH to 11, added 500g of diatomaceous earth, stirred and decolorized under normal pressure for 5min, filtered while it was hot, and cooled the filtrate to 15- 20°C, add seed crystals and stand for crystallization for 3 hours, then stand for crystallization at 0-10°C for 3 hours, -10-0°C for 4 hours, filter, and dry the solid in vacuum at 40-50°C for 8 hours to obtain Orange-yellow sodium bromophenolate 10.2kg, yield 90.6%, purity 100% (HPLC method).

Embodiment 3

[0037] Put 40L of 80% methanol, 1.9kg (47.5mol) of sodium hydroxide, and 10kg of 7-(4-bromobenzoyl)-1,3-dihydro-2H-indol-2-one into the pressurized reactor in sequence (31.6mol), react at 100°C for 4h under closed stirring, cool down to 20-30°C, add hydrochloric acid dropwise to adjust the pH to 11, add 500g of neutral alumina, stir and decolorize under normal pressure for 10min under reflux, filter while hot, and cool the filtrate to 15 ~20°C, add seed crystals and stand for crystallization for 2h, then stand for crystallization at 0~10°C for 3h, -10~0°C for 4h, filter, and dry the solid in vacuum at 40~50°C for 6h, that is 9.9 kg of orange-yellow sodium bromophenolate was obtained, with a yield of 88.0% and a purity of 100% (HPLC method).

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Abstract

The invention discloses a method for preparing bromfenac sodium and relates to the technical field of medicinal chemical industry. The method comprises the following steps: adding 7-(4-bromobenzoyl)-1,3-dihydro-2H-indolyl-2-one and sodium hydroxide into a monoalcohol-deionized water system, carrying out a closed stirred reaction for 3 to 5 hours at the temperature of 90 DEG C to 110 DEG C, carrying out cooling, dropwise adding hydrochloric acid to adjust pH, adding a decolorant, carrying out refluxing-stirring decolorization under atmospheric pressure, carrying out filtering while the solutionis hot, and carrying out crystallization and drying, thereby obtaining bromfenac sodium. According to the method, the monoalcohol-deionized water system serves as a reaction solvent and replaces mixed solvents of water-soluble organic solvents/water-insoluble organic solvents in the prior art such as toluene/ethanol and dichloromethane/ethanol; through changing a solvent system of a bromfenac sodium synthesis reaction, process operations are simplified, and the product yield is increased; a decolorization process is integrated into a reaction aftertreatment process, so that the product purityis improved while decolorization is carried out, the production cost is reduced, and the product purity can reach 100% through HPLC measurement; and the reaction solvent can be recycled, and the harmless treatment cost of the solvent is low.

Description

technical field [0001] The invention relates to the technical field of medicine and chemical industry, in particular to a preparation method of bromfenac sodium. Background technique [0002] Bromfenac sodium (Bromfenac sodium sesquihydrate), the chemical name is 2-amino-3-(4-bromobenzoyl) phenylacetic acid sodium salt sesquihydrate, developed by Japan Senju Pharmaceutical Company, its preparation is 0.1% bromfenac Sodium eye drops were first launched in Japan in 2000 (trade name: Specification: 5ml / bottle), launched in the United States in 2005. Bromfenac sodium is a non-steroidal anti-inflammatory drug, which is mainly used clinically for the symptomatic treatment of inflammatory diseases of the outer eye and anterior eye, such as: blepharitis, conjunctivitis, and strong meningitis (including the upper strong membrane). inflammation), postoperative inflammation, etc. [0003] The synthetic route of bromfenac sodium is less, and the typical synthetic method is that 7-(4...

Claims

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Application Information

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IPC IPC(8): C07C227/20C07C229/42
CPCC07C227/20C07C229/42
Inventor 吴标凌林黄德武戴一
Owner HEFEI JIUNUO MEDICAL TECH
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