Preparation method of canrenone

A technology of canrenone and compounds, which is applied in the field of drug synthesis, can solve the problems of difficult complete reaction of products, low yield and purity, and achieve the effects of reduced side reactions, high yield, and reduced production costs

Inactive Publication Date: 2018-05-15
GUANGXI WANDE PHARMA
View PDF3 Cites 4 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] In the described reaction route, the ring-forming esterification reaction of the E ring is carried out first, and then the dehydrogenation reaction is carried out. When the product is treated with sodium hydroxide, the lactone will be hydrolyz...

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 canrenone
  • Preparation method of canrenone
  • Preparation method of canrenone

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0024] A kind of preparation method of canrenone, concrete experimental operation is as follows:

[0025] Under the protection of inert gas, add organic solvent, sodium ethoxide, diethyl malonate, and catalyst I to the reactor in sequence, stir for 0.3-1h, add compound I, keep warm for 4-7h, TLC shows that after the reaction is complete , lower the temperature to -5~5°C, add acid to adjust the pH to 7.0~7.2, concentrate most of the solvent under reduced pressure, add toluene to concentrate to dryness, then add toluene as the reaction solvent, transfer the reaction solution to the autoclave, add water, after sealing, replace the air with nitrogen, raise the temperature, after the reaction is complete, concentrate to dry toluene, add water to stir, suction filter, and dry to obtain canrenone.

[0026] Wherein: the volume mass ratio of diethyl malonate and compound I is diethyl malonate:compound I=(0.6~1.2)V:1W;

[0027] The volume mass ratio of sodium ethylate to compound I is ...

Embodiment 1

[0038] A preparation method of canrenone, the technical process is as follows:

[0039] The specific experimental steps are as follows:

[0040] Under the protection of nitrogen, add 150ml of ethanol and 15g of sodium ethoxide to the three-necked flask, raise the temperature to 78°C, add 18ml of diethyl malonate, 0.15g of potassium dihydrogen phosphate, stir for 0.3h, add 30g of compound Ⅰ, keep the temperature for 4h, TLC (PE:EA=4:1) showed that the reaction was complete, lowered the temperature to -5°C, added an appropriate amount of glacial acetic acid to adjust the pH to 7.0, concentrated most of the solvent, added toluene to recover the remaining solvent, added 150ml of toluene, and transferred to In the autoclave, add 15ml of water, seal it and replace it with nitrogen three times, raise the temperature to 100°C, react for 24 hours, and the pressure is 2.5kg. After TLC (PE: EA = 4:1) shows that the reaction is complete, cool down, concentrate to viscous, add water to con...

Embodiment 2

[0042] A preparation method of canrenone, the technical process is as follows:

[0043] The specific experimental steps are as follows:

[0044] Under the protection of helium, add 150ml of methanol, 150ml of ethanol, 15g of sodium ethoxide into the three-necked flask, heat up to 78°C, add 60ml of diethyl malonate, 0.25g of potassium dihydrogen phosphate, stir for 0.5h, add 50g of compound Ⅰ, Insulate the reaction for 5 hours, TLC (PE:EA=4:1) shows that the reaction is complete, lower the temperature to 0°C, add an appropriate amount of glacial acetic acid to adjust the pH to 7.1, concentrate most of the solvent, add toluene to recover the remaining solvent, add 300ml of toluene , transfer to an autoclave, add 35ml of water, replace with helium three times after sealing, heat up to 120°C, pressure 3kg, react for 20h, TLC (PE:EA=4:1) shows that the reaction is complete, cool down, concentrate to viscous, Add water and continue to dry toluene, add appropriate amount of water an...

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 preparation method of canrenone. The preparation method comprises the following steps: synthesizing canrenone by using a dehydrogenation product compound I as a substrate, adding a catalyst, carrying out an internal esterification reaction, and optimizing a reaction line. After the reaction is completed, the product is adjusted to be neutral and is directly concentrated, and a high pressure reaction is carried out directly after a dry solvent is recycled by using methylbenzene with ethyl alcohol, so that the aftertreatment reaction steps are reduced, the hydrolysis ofan E-ring ethyl formate group is avoided, and the high-pressure reaction difficulty is greatly lowered. The operability of the reaction is greatly improved, the production cost is reduced, the side reactions are greatly reduced, the reaction of each step is relatively easy to realize, the yield is greatly improved, the production is more economical and safer, and the preparation method is more applicable for industrial production.

Description

technical field [0001] The invention relates to the field of drug synthesis, in particular to a preparation method of canrenone. Background technique [0002] Canrenone, chemically named 17β-hydroxy-3-oxo-17α-pregna-4,6-diene-21-carboxylic acid-Y-lactone, is a commonly used diuretic and is also a synthetic aldosterone An important intermediate of the receptor antagonist spironolactone. Canrenone can also be widely used in the preparation of important steroid raw materials such as eplerenone and other cardiovascular disease drugs. There is a synthetic route reported in the patent US3919198: 4-androstenedione is used as a substrate to obtain canrenone through the following reaction: [0003] [0004] In the described reaction route, the ring-forming esterification reaction of the E ring is carried out first, and then the dehydrogenation reaction is carried out. When the product is treated with sodium hydroxide, the lactone will be hydrolyzed to open the ring, and the ethy...

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): C07J21/00
CPCC07J21/003
Inventor 杨坤李家宝周鸿
Owner GUANGXI WANDE 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