Preparation method of 16a,17a-dyhydroxyl-21-acetoxyl-1,4-pregnene diene-3,11,20-triketone

A kind of technology of gestodene and acetoxy, which is applied in the field of preparation of 16a,17a-dihydroxy-21-acetoxy-1,4-gestodene-3,11,20-trione, can Solve problems such as many side reactions, unpublished products complying with the European Pharmacopoeia, and complex products

Inactive Publication Date: 2015-03-25
CHONGQING UNIV OF POSTS & TELECOMM
View PDF6 Cites 3 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] U.S. Patent 4695625 discloses a chemical synthesis method for preparing budesonide by using 16a-hydroxyprednisolone as a raw material through a one-step reaction, but the raw material price of this method is high, and how to control the reaction conditions is not announced so that the product meets the requirements of the European Pharmacopoeia; China Patent 101279997 B has announced the synthesis process route of preparing budesonide with prednisolone acetate as the starting raw material. Although the reaction steps are short, due to the selection of raw materials and the setting of reaction conditions, the elimination and oxidation reaction time is...

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
  • Preparation method of 16a,17a-dyhydroxyl-21-acetoxyl-1,4-pregnene diene-3,11,20-triketone
  • Preparation method of 16a,17a-dyhydroxyl-21-acetoxyl-1,4-pregnene diene-3,11,20-triketone

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0017] 1) In a 500ml dry reaction flask, add 35.8g raw material prednisone (0.1mol), 70ml ethyl acetate, 71.6ml acetic anhydride, 0.35g p-toluenesulfonic acid, install a reflux condenser, under nitrogen protection Stir and heat up and control the temperature at 70°C for 2h. After the reaction was detected by TLC, it was cooled to room temperature, ethyl acetate was evaporated, then washed with 100ml of water, filtered, and the filter cake was dried at low temperature to obtain a crude product, which was separated and purified to obtain a white solid powder A (17a, 21-diacetoxy- 1,4-pregnadiene-3,11,20-trione) 42g, yield 95%, mp: 225-226°C.

[0018] 2) Dissolve 42g of potassium acetate in 220ml of DMF and distill to remove water and a small amount of low-boiling impurities. After the distilled DMF reaches the constant boiling point, cool the mixture to 100°C and then add the reaction product A42g (0.095 mol) and 200ml DMF solution, reacted at 105°C for 5h. TLC tracking detect...

Embodiment 2

[0022] 1) In a 500ml dry reaction flask, add 50g raw material prednisone (0.14mol), 100ml ethyl acetate, 100ml acetic anhydride, 0.48g p-toluenesulfonic acid, install a reflux condenser, stir and heat up under nitrogen protection And the temperature was controlled at 60°C for 4h. After TLC detection, the reaction was cooled to room temperature, ethyl acetate was evaporated, then washed with 150ml of water, filtered, and the filter cake was dried at low temperature to obtain a crude product, which was separated and purified to obtain a white solid powder A (17a, 21-diacetoxy- 1,4-pregnadiene-3,11,20-trione) 53.8g, yield 87%.

[0023] 2) Add 53.8 intermediate A (0.12mol), 250ml DMF, and 27g potassium acetate into a three-necked flask, stir and heat to 90°C for 7 hours, and TLC traces and detects that the reaction is complete. After cooling down to room temperature, the reaction solution was slowly poured into 300ml of ice water with stirring, and an off-white powder was precipi...

Embodiment 3

[0027] 1) In a 500ml dry reaction flask, add 60g raw material prednisone (0.17mol), 120ml ethyl acetate, 120ml acetic anhydride, 0.48g p-toluenesulfonic acid, install a reflux condenser, stir and heat up under nitrogen protection And the temperature was controlled at 80°C for 2h. After TLC detection, the reaction was cooled to room temperature, ethyl acetate was evaporated, then washed with 150ml of water, filtered, and the filter cake was dried at low temperature to obtain a crude product, which was separated and purified to obtain a white solid powder A (17a, 21-diacetoxy- 1,4-pregnadiene-3,11,20-trione) 67.8g, yield 90.3%.

[0028] 2) Add 67.8g of intermediate A (0.154mol), 300ml of DMF, and 67.8g of sodium acetate into a three-neck flask, stir and heat to 90°C for 7 hours, and TLC traces and detects that the reaction is complete. After cooling down to room temperature, the reaction solution was slowly poured into 300ml of ice water with stirring, and an off-white powder w...

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
Yieldaaaaaaaaaa
Login to view more

Abstract

The invention provides a preparation method of 16a,17a-dyhydroxyl-21-acetoxyl-1,4-pregnene diene-3,11,20-triketone. The preparation method comprises the following steps: step 1, by taking prednisone as a raw material, allowing the prednisone to have an esterification reaction with acetic oxide; step 2, performing a degreasing reaction by use of alkali; and step 3, oxidizing by use of potassium permanganate under an acidic condition. The method has the advantages of adopting raw materials which are low in cost and easy to obtain, simplifying the production process route and being simple to operate and suitable for large-scale industrial production.

Description

technical field [0001] The present invention relates to a preparation method of 16a, 17a-dihydroxy-21-acetoxy-1,4-pregnadiene-3,11,20-trione. Background technique [0002] 16a,17a-Dihydroxy-21-acetoxy-1,4-pregnadiene-3,11,20-trione is an intermediate in the synthesis of the anti-inflammatory drug budesonide. [0003] U.S. Patent 4695625 discloses a chemical synthesis method for preparing budesonide by using 16a-hydroxyprednisolone as a raw material through a one-step reaction, but the raw material price of this method is high, and how to control the reaction conditions is not announced so that the product meets the requirements of the European Pharmacopoeia; China Patent 101279997 B has announced the synthesis process route of preparing budesonide with prednisolone acetate as the starting raw material. Although the reaction steps are short, due to the selection of raw materials and the setting of reaction conditions, the elimination and oxidation reaction time is long and th...

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): C07J5/00
CPCC07J5/0061
Inventor 冉亚玲陈义文
Owner CHONGQING UNIV OF POSTS & TELECOMM
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