A kind of preparation method of bromfenac sodium

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

Active Publication Date: 2021-06-01
HEFEI JIUNUO MEDICAL TECH
View PDF0 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

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 hydrolysis. The existing processes all use mixed solvents, and the solvents cannot Recycling, high cost of environmental protection treatment

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • A kind of preparation method of bromfenac sodium
  • A kind of preparation method of bromfenac sodium
  • A kind of preparation method of bromfenac sodium

Examples

Experimental program
Comparison scheme
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).

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

PropertyMeasurementUnit
wavelengthaaaaaaaaaa
Login to view more

Abstract

The invention discloses a preparation method of bromfenac sodium, relates to the technical field of medicine and chemical industry, comprising the following steps: preparing 7-(4-bromobenzoyl)-1,3-dihydro-2H-indole-2- Put the ketone and sodium hydroxide into the monohydric alcohol-deionized water system, stir and react in a closed manner at 90-110°C for 3-5 hours, cool down, add hydrochloric acid dropwise to adjust the pH, add decolorizer, reflux under normal pressure to decolorize, filter while hot, and analyze Crystallize and dry to obtain sodium bromophenolate. In the present invention, the mixed solvent of water-soluble organic solvents / water-insoluble organic solvents such as substituted toluene / ethanol, dichloromethane / ethanol etc. in the prior art is replaced with monohydric alcohol-deionized water system as reaction solvent, by changing the synthesis of bromfenac sodium The solvent system in the reaction simplifies the process operation, improves the product yield, and integrates the decolorization process into the post-reaction treatment process, which improves the product purity while decolorizing and saves production costs. The product purity can reach 100% as determined by HPLC. In addition, the reaction solvent can be recycled, and the cost of harmless disposal 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

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Application Information

Patent Timeline
no application Login to view more
Patent Type & Authority Patents(China)
IPC IPC(8): C07C227/20C07C229/42
CPCC07C227/20C07C229/42
Inventor 吴标凌林黄德武戴一
Owner HEFEI JIUNUO MEDICAL TECH
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap