Method for preparing 17 alpha-hydroxyl-3-oxo-gamma-lactone-pregnene-4-alkene-(7 alpha, 9 alpha)-dicarboxylic acid lactone

A technology of dicarboxylic acid and lactone, applied in the direction of steroids, organic chemistry, etc., can solve the problems of complex process and low efficiency, and achieve the effect of simple process and high production efficiency

Inactive Publication Date: 2016-05-04
ZHEJIANG XIANJU PHARMA
View PDF2 Cites 1 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] The purpose of the present invention is to solve the complex process and low efficiency of the method currently u

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 17 alpha-hydroxyl-3-oxo-gamma-lactone-pregnene-4-alkene-(7 alpha, 9 alpha)-dicarboxylic acid lactone
  • Method for preparing 17 alpha-hydroxyl-3-oxo-gamma-lactone-pregnene-4-alkene-(7 alpha, 9 alpha)-dicarboxylic acid lactone

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0041] The first step, the synthesis of compound II;

[0042] Add compound I (10g, 0.024mol), triethylamine (6mL, 0.0432mol) and dichloromethane (60ml) into the three-necked flask, stir and dissolve, cool down to -10°C~-5°C, and maintain the temperature Slowly add methanesulfonyl chloride (3mL, 0.0388mol) dropwise. After the addition is complete, keep the reaction for 0.5~1h, and use thin-layer chromatography (TLC) to ensure that the raw materials are completely reacted, then concentrate under reduced pressure to dryness, and the oily yellow compound II is obtained. , the weight is about 11.6g, and the yield is 97.7%.

[0043] The second step, the synthesis of 17α-hydroxy-3-oxo-γ-lactone-pregn-4-ene-(7α, 9α)-dicarboxylic acid lactone;

[0044] Add 50mL of acetic acid / water (1:4) and sodium acetate (5g, 0.0609mol) into a three-neck flask, raise the temperature to 40°C-50°C, stir for 30min, then add compound II (10g, 0.0202mol) into it, and raise the temperature to 110°C, keep...

Embodiment 2

[0056] The first step, the synthesis of compound II:

[0057] Add compound I (10g, 0.024mol), triethylamine (6mL, 0.0432mol) and chloroform (60ml) into the three-necked flask, stir and dissolve, cool down to -10°C~-5°C, and slowly drop Add methanesulfonyl chloride (3mL, 0.0388mol). After the addition, keep it warm for 0.5~1h, and use TLC method to ensure that the raw materials are completely reacted, then concentrate under reduced pressure and close to dryness to obtain 10.64g of oily yellow compound II, with a yield of 93.8 %.

[0058] The second step, the synthesis of compound A:

[0059] Add 40mL of acetic acid / water (1:3) and sodium hydroxide (4g, 0.099mol) into a three-necked flask, raise the temperature to 40~50°C, stir for 30min, then add compound II (10g, 0.0202mol), and raise the temperature to 110 ~120°C, keep warm for 6 hours, and use TLC method to ensure the complete reaction of the raw materials. After cooling to 25°C, add 30mL of dichloromethane and 30mL of wat...

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 17alpha-hydroxyl-3-oxo-gamma-lactone-pregnene-4-alkene-(7alpha,9alpha)-dicarboxylic acid lactone. Firstly, a compound I dissolved in a solvent and methanesulfonyl chloride are subjected to 11-hydroxyl sulfonylation reaction under the action of an acid-binding agent, and a compound II is obtained; then the compound II and inorganic alkali are added into the solvent and react to obtain the target compound 17alpha-hydroxyl-3-oxo-gamma-lactone-pregnene-4-alkene-(7alpha,9alpha)-dicarboxylic acid lactone; finally, the target product high in purity is obtained through re-crystallization and column chromatography. The 17alpha-hydroxyl-3-oxo-gamma-lactone-pregnene-4-alkene-(7alpha,9alpha)-dicarboxylic acid lactone can be prepared to serve as a reference substance, and accordingly the quality of eplerenone can be better controlled.

Description

technical field [0001] The present invention relates to a preparation method of eplerenone 7, 9 lactonization by-products, in particular to a 17α-hydroxyl-3-oxo-γ-lactone-pregn-4-ene-(7α, 9α) Process for the preparation of dicarboxylic lactones. Background technique [0002] Eplerenone is a selective aldosterone receptor antagonist that acts only on mineralocorticoid receptors, but not on androgen and progesterone receptors. Eplerenone is widely used in the treatment of hypertension and other cardiovascular diseases, especially for the treatment of hypertension. 17α-Hydroxy-3-oxo-γ-lactone-pregn-4-ene-(7α,9α)-dicarboxylic acid lactone is a by-product of eplerenone 7,9-position lactonization, its chemical The structural formula is as follows: [0003] . [0004] The European Pharmacopoeia (EP8.0) records this substance as an impurity of eplerenone, but the content of this substance in the reaction process of eplerenone is 1-4%, so it is difficult to separate and purify....

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): C07J71/00
CPCC07J71/0005
Inventor 金宁石成灿
Owner ZHEJIANG XIANJU PHARMA
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