Novel synthetic method of high-purity florfenicol

A florfenicol and high-purity technology, applied in the new field of high-purity florfenicol synthesis, can solve the problem that the finished product cannot meet the high-standard florfenicol finished product, the high-purity florfenicol has high cost, and the single impurity exceeds the standard. Solvent and other problems, to achieve the effect of low cost, less impurities and shortened process steps

Inactive Publication Date: 2014-08-13
京山瑞生制药有限公司 +1
View PDF6 Cites 11 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Due to the high impurity content of the crude product and the dark color of such finished products, the refined finished products still contain a large amount of impurities, often appear too dark in color, poor solubility, excessive single impurity and solvent exceed the standard, so that the finished product cannot meet the high requirements. Specifications Requirements for finished products o

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
  • Novel synthetic method of high-purity florfenicol
  • Novel synthetic method of high-purity florfenicol
  • Novel synthetic method of high-purity florfenicol

Examples

Experimental program
Comparison scheme
Effect test

Example Embodiment

[0031] Example 1

[0032] Dissolve 33 grams of diethylamine in 330 milliliters of dichloromethane, cool down to -20°C, keep stirring at a temperature, slowly feed 75 grams of hexafluoropropylene, keep stirring for half an hour after passing, transfer to a 1-liter high-pressure reactor, add 100 g D-threo-2-(dichloromethyl)-4,5-dihydro-5-[p-(methylsulfonyl)phenyl]-4-oxazole methanol, the temperature was raised to 100℃, the pressure in the kettle was 0.55MPa, the reaction was incubated for 2 hours, and a batch of fluorine substitution reaction solution was taken out. The fluorine-substituted reaction solution was first washed with 500 ml of 10% aqueous sodium carbonate solution, stirred for 0.5 hour, left to stand for stratification, the organic phase was washed with 500 ml of water, washed until the pH of the reaction solution was 7, after atmospheric distillation of part of the solvent, the temperature was lowered. Crystallization, the crystals were filtered at 0 °C to obtain ...

Example Embodiment

[0033] Example 2

[0034] Dissolve 33 grams of diethylamine in 330 milliliters of dichloromethane, cool down to -20°C, keep stirring at a temperature, slowly feed 75 grams of hexafluoropropylene, keep stirring for half an hour after passing, transfer to a 1-liter high-pressure reactor, add 100 g D-threo-2-(dichloromethyl)-4,5-dihydro-5-[p-(methylsulfonyl)phenyl]-4-oxazole methanol, the temperature was raised to 100℃, the pressure in the kettle was 0.55MPa, the reaction was incubated for 2 hours, and a batch of fluorine substitution reaction solution was taken out. The fluorine substitution reaction solution was first washed with 500 ml of a 10% aqueous sodium acetate solution, stirred for 0.5 hour, left to stand for stratification, the organic phase was washed with 500 ml of water, washed until the pH of the reaction solution was 7, after atmospheric distillation of part of the solvent, the temperature was lowered. Crystallization, the crystals were filtered at 0 °C to obtain...

Example Embodiment

[0035] Example 3

[0036] Dissolve 33 grams of diethylamine in 330 milliliters of dichloromethane, cool down to -20°C, keep stirring at a temperature, slowly feed 75 grams of hexafluoropropylene, keep stirring for half an hour after passing, transfer to a 1-liter high-pressure reactor, add 100 g D-threo-2-(dichloromethyl)-4,5-dihydro-5-[p-(methylsulfonyl)phenyl]-4-oxazole methanol, the temperature was raised to 100℃, the pressure in the kettle was 0.55MPa, the reaction was incubated for 2 hours, and a batch of fluorine substitution reaction solution was taken out. The fluorine substitution reaction solution was first washed with 500 milliliters of 10% aqueous sodium bicarbonate solution, stirred for 0.5 hour, left to stand for stratification, the organic phase was washed with 500 milliliters of water, washed until the pH of the reaction solution was 7, after atmospheric distillation of part of the solvent, Cooling and crystallization, the crystals were filtered at 0°C to obta...

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 provides a novel synthetic process of high-purity florfenicol. The process comprises the following steps: by taking a compound D-threo form-2-(dichloromethyl)-4,5-dihydro-5-[p-(methylsulfonyl)phenyl]-4-oxazole methanol as an initial raw material, carrying out fluoro-substitution by using an Ishikawa reagent; crystallizing and purifying to obtain a high-purity fluoro product (4S,5S)-2-(dichloracetyl)-4-(methyl fluoride)-5-[4-(methylsulfonyl)phenyl]-4, 5-dihydrooxazole; and further carrying out a hydrolysis reaction directly on the high-purity fluoro product without being added into an organic solvent to directly obtain a high purity florfenicol product. According to the production process, the fluoro intermediate product is crystallized and purified to obtain a high purity product by adopting a direct hydrolysis process without using the organic solvent, so that the novel synthetic method is simple in process operation, environmental friendly, high in product purity, few in impurity, free from solvent residue and low in cost.

Description

technical field [0001] The invention relates to a chemical synthesis method, in particular to a new synthesis method of high-purity florfenicol. Background technique [0002] Florfenicol, molecular formula: C 12 h 14 CL 2 FNO 4 S, molecular weight: 358.2, CAS No.: 73231-34-2, its structural formula is as follows: [0003] [0004] Florfenicol (Florfenicol) Chinese name: fluprofen; An antibacterial drug that can be used to treat infections caused by Gram-positive bacteria, Gram-negative bacteria, and Rickettsiae. It was first launched in Japan in 1990. In 1993, Norway approved the drug to treat salmon furunculosis. In 1995, France, the United Kingdom, Austria, Mexico and Spain approved it to treat bovine respiratory system bacterial diseases. It is also approved as a feed additive for pigs in Japan and Mexico to prevent and treat bacterial diseases in pigs. [0005] There have been many reports on the synthesis and production methods of Florfenicol. Nagabhushan of ...

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): C07C317/32C07C315/04
Inventor 张治国钟旭辉张伟略谢娜
Owner 京山瑞生制药有限公司
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