Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Synthesis method of bromfenac sodium

A technology of bromfenac sodium and its synthesis method, which is applied in the field of drug synthesis, can solve problems such as explosion or personnel poisoning, high toxicity, and excessive heavy metals, and achieve the effects of less environmental pollution, good environmental protection, and mild and controllable reaction conditions

Pending Publication Date: 2022-07-12
郑州灏瑞医药科技有限公司
View PDF11 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0019] This method is also the mainstream synthesis route for the domestic production of bromfenac sodium, but manganese dioxide is used in the synthesis process, which may easily lead to excessive heavy metals in the finished product
Boron trichloride and N-bromosuccinimide (NBS) are also used in the synthesis process, which are high-risk chemicals. N-bromosuccinimide (NBS) has high toxicity and is easy to produce during the preparation process. cause explosion or poisoning

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
  • Synthesis method of bromfenac sodium
  • Synthesis method of bromfenac sodium
  • Synthesis method of bromfenac sodium

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0053] The synthetic method of bromfenac sodium of the present invention, the detailed steps of this synthetic method are as follows:

[0054] a. Preparation of 2-(9-fluorenemethoxycarbonylamino)benzoic acid:

[0055] First, add solvent isopropyl ether 1600g, triethylamine 111g and anthranilic acid 137g (1mol) into a 5L reaction flask for stirring and dissolving; then cool down to 0°C, take 284.6g of fluorene methoxycarbonyl chloride and dissolve in 1000g of isopropyl ether , the obtained fluorene methoxycarbonyl chloride isopropyl ether solution was slowly added dropwise to the reaction flask, which lasted for 30min; after the dropwise addition was completed, the reaction was continued to stir at 0°C for 2h; after the reaction was completed, the filtrate was filtered, and 80% of the solvent was removed under reduced pressure, and the residue 2 kg of water was added to the mixture, and the temperature was kept at 0°C for 2 hours for crystallization. After crystallization, filt...

Embodiment 2

[0065] The synthetic method of bromfenac sodium of the present invention, the detailed steps of this synthetic method are as follows:

[0066] a. Preparation of 2-(9-fluorenemethoxycarbonylamino)benzoic acid:

[0067] First, 1370 g of isopropyl ether, 101 g of triethylamine and 137 g (1 mol) of anthranilic acid were added to a 5L reaction flask for stirring and dissolving, and the temperature was lowered to 0°C. Fluorene methoxycarbonyl chloride isopropyl ether solution was slowly added dropwise to the reaction flask, which lasted 30 min; after the dropwise addition was completed, the reaction was continued to stir at 0 °C for 2 h; after the reaction was completed, the filtrate was filtered, and 80% of the solvent was removed from the filtrate under reduced pressure. 2kg of water was incubated at 0°C for 2h for crystallization, and filtered after crystallization, and the obtained solid was dried at 60°C for 3h to obtain 294.8g (0.82mol) of 2-(9-fluorenylmethoxycarbonylamino)be...

Embodiment 3

[0077] The synthetic method of bromfenac sodium of the present invention, the detailed steps of this synthetic method are as follows:

[0078] a. Preparation of 2-(9-fluorenemethoxycarbonylamino)benzoic acid:

[0079] First, 2055g of isopropyl ether, 121g of triethylamine and 137g (1mol) of anthranilic acid were added to a 5L reaction flask for stirring and dissolving, and the temperature was lowered to 0°C; The fluorene methoxycarbonyl chloride isopropyl ether solution was slowly added dropwise to the reaction flask, which lasted 30 min; after the dropwise addition, the reaction was continued at 0 °C for 2 h; after the reaction was completed, the filtrate was filtered, and 80% of the solvent was removed from the obtained filtrate under reduced pressure. Add 2kg of water, keep at 0°C for 2h for crystallization, filter after crystallization, and dry the obtained solid at 60°C for 3h to obtain 310g (0.86mol) of 2-(9-fluorenylmethoxycarbonylamino)benzoic acid;

[0080] b, prepar...

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

No PUM Login to View More

Abstract

The invention discloses a synthesis method of bromfenac sodium. The preparation method comprises the following steps: firstly, by taking o-aminobenzoic acid as a raw material, adding a solvent, alkali and a fluorenylmethoxycarbonyl chloride isopropyl ether solution to react, and treating after the reaction to obtain 2-(9-fluorenylmethoxycarbonyl amino) benzoic acid; adding a solvent and strongly acidic cationic resin into the obtained product for reaction, and treating after the reaction to obtain 2-(9-fluorenylmethoxycarbonyl amino) ethyl benzoate; then a solvent, 4-bromobenzoyl chloride and a catalyst are added for a reaction, and 3-(4-bromo-benzoyl)-2-(9-fluorenylmethoxycarbonyl amino)-ethyl benzoate is obtained through treatment after the reaction; adding a solvent and a sodium hydroxide aqueous solution into the obtained product for reaction and treatment to obtain a bromfenac sodium crude product; and finally, refining the obtained bromfenac sodium crude product to obtain a bromfenac sodium product. The preparation method has the advantages of easily available raw materials, mild reaction conditions and high purity of the prepared finished product, and is suitable for industrial production.

Description

1. Technical field: [0001] The invention belongs to the technical field of drug synthesis, and in particular relates to a method for synthesizing bromfenac sodium. 2. Background technology: [0002] Bromfenac sodium, chemical name is 2-amino-3-(4-bromobenzoyl) phenylacetate sodium, its structure is similar to ketoprofen and diclofenac, it is the most effective cyclooxygenase inhibitor One of them is that it can inhibit the synthesis of prostaglandin inflammatory mediators mediated by cyclooxygenase, and has a strong anti-inflammatory and analgesic effect, which is 10 times stronger than other non-steroidal anti-inflammatory drugs. At present, it is mainly used clinically as an anti-inflammatory eye drop for the symptomatic treatment of inflammatory diseases of the outer eye and the anterior eye. [0003] [0004] At present, the synthetic method of bromfenac sodium mainly includes the following several: [0005] US patent document US4126635.US4182774 and document "Journ...

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
IPC IPC(8): C07C229/42C07C227/20C07C227/40C07C227/42
CPCC07C227/20C07C227/40C07C227/42C07C269/06C07C269/04C07C2603/18C07C229/42C07C271/28Y02P20/55
Inventor 毛影朱赞梅刘志庆娄丽丽赵青候菊红朱向可
Owner 郑州灏瑞医药科技有限公司
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

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

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com