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

Method for preparing 9,11beta-epoxy steroid compound

A technology of epoxy steroids and compounds, which is applied in the field of preparation of key intermediates 9,11β-epoxy steroids, and can solve problems affecting product quality and yield

Inactive Publication Date: 2014-02-19
AURISCO PHARMACEUTICAL CO LTD
View PDF5 Cites 7 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

But above-mentioned method can generate 2-5% organic impurity in epoxy and hydrolysis process, has influenced the quality and the yield of product, therefore, needs further improvement

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 9,11beta-epoxy steroid compound
  • Method for preparing 9,11beta-epoxy steroid compound
  • Method for preparing 9,11beta-epoxy steroid compound

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0054] Example 1: 16β-methyl-9α-bromo-11β-formyloxy-1,4-diene-pregna-11β,17α,21-trihydroxy-3,20-dione-21-b Preparation of esters

[0055]

[0056] Put 10.0g of 16β-methyl-1,4,9-triene-pregna-17α,21-dihydroxy-3,20-diketone-21-acetate and 35.0g of DMF under nitrogen protection , cooled to 0°C, and kept the temperature not exceeding 5°C, add 3.6g of 70% perchloric acid aqueous solution dropwise, and add 5.0g of DBH in 3 times. After reacting for 2 hours, no raw material point was detected by HPLC, 30 g of methanol was added, and stirred for half an hour. Pour the reaction solution into 300g of ice-water mixture, stir at 0-5°C for 1 hour, filter with suction, and dry the filter cake under vacuum at 40°C to obtain 13.0g of 16β-methyl-9α-bromo-11β-formyloxy-1 , 4-diene-pregna-11β,17α,21-trihydroxy-3,20-dione-21-acetate (Formula 3.1), HPLC99.5%.

Embodiment 2

[0057] Example 2: Preparation of 16β-methyl-9,11β-epoxy-1,4-diene-pregna-17α,21-dihydroxy-3,20-dione

[0058]

[0059] Put in 16β-methyl-9α-bromo-11β-formyloxy-1,4-diene-pregna-11β,17α,21-trihydroxy-3,20-dione of formula 3.1 under nitrogen protection 10.0 g of -21-acetate, 100 g of DCM, and 20 g of methanol were cooled to -5°C. 40% sodium hydroxide aqueous solution containing 3.0 g of sodium hydroxide was added dropwise, and the temperature was controlled at -5-0°C to keep the reaction for 2 hours. After no raw material was detected by HPLC, 8 g of glacial acetic acid was added dropwise. Concentrate under reduced pressure at 40°C until the remaining 25g, pour the reaction solution into 200g of ice-water mixture, stir at 0-5°C for 1 hour, and filter with suction to obtain 7.0g of wet crude product. Add the wet crude product, 170g of DCM, and 25g of methanol, stir and heat up to reflux, reflux for half an hour, and heat filter. The filtrate was concentrated under normal pre...

Embodiment 3

[0060] Example 3: Preparation of 16β-methyl-9,11β-epoxy-1,4-diene-pregna-17α,21-dihydroxy-3,20-dione

[0061]

[0062] Put in 16β-methyl-9α-bromo-11β-formyloxy-1,4-diene-pregna-11β,17α,21-trihydroxy-3,20-dione of formula 3.1 under nitrogen protection 10.0 g of -21-acetate and 200 g of methanol were cooled to 0°C. 25% methanol solution containing 2.5g of sodium hydroxide was added dropwise, and the temperature was controlled at 0-5°C to keep the reaction for 2 hours. After HPLC detected that there was no raw material, 8g of glacial acetic acid was added dropwise. Concentrate under reduced pressure at 40°C until about 25g remains, pour the reaction solution into 200g of ice-water mixture, stir at 0-5°C for 1 hour, and filter with suction to obtain 7.0g of wet crude product. Add the wet crude product, 170g of DCM, and 25g of methanol, stir and heat up to reflux, reflux for half an hour, and heat filter. The filtrate was concentrated under normal pressure to an internal tempe...

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 present invention provides a method for preparing a 9,11beta-epoxy steroid compound represented by a formula 1. According to the method, a 9,11-double bond-21-ester steroid compound is adopted as a raw material, and reacts with a halogenating agent in a suitable organic solvent containing 70% perchloric acid to produce a 9alpha-halo-11beta-ester-21-ester steroid compound, and the 9alpha-halo-11beta-ester-21-ester steroid compound reacts with a strong base in an organic solvent to obtain the 9,11beta-epoxy steroid compound. The 9,11beta-epoxy steroid compound can be used for preparation of dexamethasone, betamethasone and series other drugs. According to the present invention, the 9,11beta-epoxy steroid compound can be prepared from the almost equimolar amount of the 9,11-double bond-21-ester steroid compound, such that the method is the synthesis method with characteristics of economy, efficiency and environmental protection.

Description

technical field [0001] The present invention relates to medicinal chemistry, in particular to a preparation method of a pharmaceutical intermediate, in particular to a preparation method of a key intermediate 9,11β-epoxy steroid used in the preparation of dexamethasone and betamethasone series medicines. Background technique [0002] 9,11β-epoxy steroids are key intermediates of dexamethasone series and betamethasone series of drugs, and their structural formula (Formula 1) is as follows: [0003] [0004] Dexamethasone or betamethasone can be easily prepared from 9,11β-epoxy steroids by fluorination at the 9-position, and a series of drugs can be prepared through a series of modifications at the 3-position, 6-position, 16-position, and 21-position. [0005] In Chinese patent CN101397319, a kind of 9,11β-epoxy steroid is prepared by generating halides in aliphatic alcohol, halogenated hydrocarbon, ketones or ether solvents, then using alkali to epoxidize and then hydrolyz...

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 Applications(China)
IPC IPC(8): C07J71/00
Inventor 褚定军张毅
Owner AURISCO PHARMACEUTICAL CO LTD
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