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

Method for preparing fluticasone propionate

A technology of fluticasone propionate and formula, which is applied in the field of medicine, can solve the problems of low product yield, difficult purification, large usage, cumbersome routes, etc., and achieve the effects of easy industrial implementation, increased reaction rate, and mild reaction conditions

Active Publication Date: 2009-10-14
湖南玉新药业有限公司
View PDF5 Cites 2 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] The route of this method is relatively cumbersome, and at the same time, silver fluoride is used in the exchange of fluorine and iodine, which is expensive, easy to deliquesce, easy to decompose when exposed to light, and the final product yield is low and difficult to purify, which limits its use in industrial production.
[0006] The world patent WO2007 / 012228 provides a method. Although the method shortens the reaction steps and avoids the use of silver fluoride, the bromofluoromethane used is expensive, and it is a gas at room temperature, with a large amount of use and high toxicity. Air pollution serious problem

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
  • Method for preparing fluticasone propionate
  • Method for preparing fluticasone propionate
  • Method for preparing fluticasone propionate

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0031] S-(chloromethyl)-6α,9α-difluoro-11β-hydroxy-16α-methyl-17α-propionyloxy-3-ketoandrost-1,4-diene-17β-thiocarboxylic acid Preparation of esters:

[0032] Add 6α, 9α-difluoro-11β-hydroxyl-16α-methyl-17α-propionyloxy-3-ketoandrost-1,4-diene-17β-thiocarboxylic acid in a 250mL three-neck flask (Fw: 468.55, 10.0g, 21.3mmol), DMF100mL, sodium bicarbonate (Fw: 84.01, 7.2g, 85.2mmol), then chlorobromomethane (Fw: 129.38, 11.0g, 85.2mmol) was added dropwise to the system at room temperature In 30min, the dropwise addition was completed, and then the system continued to stir and react at room temperature for 2h. After the reaction, the mixture in the system was poured into 500mL of water, a large amount of white solid was precipitated, filtered, the filter cake was fully washed with distilled water, and dried to obtain S-(chloromethyl)-6α,9α-difluoro-11β-hydroxyl-16α- Methyl-17α-propionyloxy-3-ketoandrost-1,4-diene-17β-thiocarboxylate (Fw: 517.03, 10.5 g, yield: 95%). HPLC conte...

Embodiment 2

[0034] S-(bromomethyl)-6α,9α-difluoro-11β-hydroxy-16α-methyl-17α-propionyloxy-3-ketoandrost-1,4-diene-17β-thiocarboxylic acid Preparation of esters:

[0035] In a 250 mL three-necked flask, 100 mL of acetone and potassium carbonate (Fw: 138.21, 8.8 g, 63.9 mmol) were sequentially added, and then dibromomethane (Fw: 173.83, 14.8 g, 85.2 mmol) was added to the system. 6α,9α-difluoro-11β-hydroxy-16α-methyl-17α-propionyloxy-3-ketoandrost-1,4-diene-17β-thiocarboxylic acid (Fw: 468.55, 10.0g, 21.3mmol) was dissolved in 50mL of acetone, and was added dropwise to the system at room temperature, and the dropwise addition was completed in about 30min, and then the system was stirred and reacted at room temperature for 4h. Warming to reflux for 1h. After the reaction was completed, the system was cooled to room temperature, most of the solvent was evaporated under reduced pressure, the mixture was poured into 300mL water, a large amount of white solid was precipitated, filtered, the fi...

Embodiment 3

[0037] S-(fluoromethyl)-6α,9α-difluoro-11β-hydroxy-16α-methyl-17α-propionyloxy-3-ketoandrost-1,4-diene-17β-thiocarboxylic acid Preparation of esters:

[0038] Anhydrous tetrabutylammonium fluoride (Fw: 261.46; 5.07g; 19.4mmol) was successively added into a 100mL dry three-necked flask, followed by [Bmim][BF 4] 20.0mL was added to the system and stirred for 5min. The S-(chloromethyl)-6α,9α-difluoro-11β-hydroxyl-16α-methyl-17α-propionyloxy-3-ketoandrost-1,4-diene- 17β-thiocarboxylic acid (Fw: 517.03, 5.0 g, 9.7 mmol) was added to the system, and then 50 mL of anhydrous acetonitrile was added to the system. The system was heated to reflux for 15h. After the reaction was completed, the system was cooled to room temperature, most of the solvent was evaporated under reduced pressure, the mixture was poured into 150mL water, a large amount of white solid was precipitated, filtered, the filter cake was washed with distilled water, dried, and then recrystallized from acetone 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 discloses a method for preparing fluticasone propionate. 6α, 9α-difluoro-11β-hydroxyl-16α-methyl-17α-propionyloxy-3-ketoandrost-1,4-diene -17β-thiocarboxylic acid reacts with bromohalomethane in a solvent in the presence of a base, then reacts the reaction product with tetraalkylammonium fluoride or M+F- in the presence of an ionic liquid and a solvent, and then Collect the target product from the reaction product. The method introduced by Fang Ming is easy to operate, high in yield, low in cost, convenient in post-treatment, and has good prospects for industrialized production.

Description

technical field [0001] The invention belongs to the technical field of medicine, and relates to a novel synthesis method for preparing fluticasone propionate. Background technique [0002] English common name of fluticasone propionate: Fluticasone Propionate; chemical name: S-(fluoromethyl)-6α, 9α-difluoro-11β-hydroxyl-16α-methyl-17α-propionyloxy-3-ketone Androst-1,4-diene-17β-thiocarboxylate. [0003] Fluticasone propionate is a topically acting corticosteroid with potent anti-inflammatory activity. When it acts locally on the nasal mucosa, no systemic effects have been detected, implying minimal hypothalamic-pituitary-adrenal inhibition. It is mainly used to treat bronchial stenosis and inflammation. [0004] At present, existing technology, such as U.S. Patent US4335121, provides a kind of method for preparing fluticasone propionate, [0005] The route of this method is relatively cumbersome, and at the same time, silver fluoride is used in the exchange of fluorine an...

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): C07J3/00
Inventor 申玉良刘喜荣谢来宾何辉贤
Owner 湖南玉新药业有限公司
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