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

Preparation method of melatonin

A technology of melatonin and methoxyl, which is applied in the field of melatonin preparation and can solve the problems of many side reactions, difficult separation of by-products, and low yield

Pending Publication Date: 2022-05-20
BAYECAO HEALTH IND RES INST (XIAMEN) CO LTD
View PDF0 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The raw materials of this method are easy to get, the price is low, the reaction conditions are relatively mild, easy to control, and there are few reaction steps, but the yield of this method is not high, the yield is only about 32%, and there are many side reactions, and the separation of byproducts is difficult.
[0006] In summary, it is not difficult to find that although there are many existing chemical synthesis methods for melatonin, they all have the disadvantage of low yield.

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 melatonin

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0026] The invention provides a method for preparing melatonin, comprising the following steps:

[0027] (1) Mix 5-methoxyindole, N,N-dimethylformamide, phosphorus oxychloride and alkaline agent, and carry out Vilsmeier-Haack formylation reaction to obtain 5-methoxyindole-3 -formaldehyde;

[0028] (2) Mix the 5-methoxyindole-3-carbaldehyde, nitromethane and a catalyst, and carry out Henry reaction to obtain 5-methoxyl-3-(2-nitrovinyl)indole;

[0029] (3) the 5-methoxy-3-(2-nitrovinyl) indole, the first reducing agent and the 5-methoxy-3-(2-nitrovinyl) indole and the second A good solvent of a reducing agent is mixed, and a carbon-carbon double bond reduction reaction is carried out to obtain 5-methoxy-3-(2-nitroethyl) indole;

[0030] (4) the 5-methoxy-3-(2-nitroethyl) indole, the second reducing agent and the 5-methoxy-3-(2-nitroethyl) indole and the first The good solvents of the two reducing agents are mixed, and the nitro reduction reaction is carried out under acidic c...

Embodiment 1

[0050] (1) Add 1.5mL phosphorus oxychloride and 10mL DMF to the reactor, and stir at 5°C for 10min; dropwise add 3g of 5-methoxyindole mixed solution dissolved in 20mL DMF solution, and the dropwise addition is completed in 20min. During the dropwise addition, the temperature was controlled at <10°C. After the dropwise addition, the reactor was controlled to stir at 35°C for 1 hour; then 12 g of ice and 30 mL of 6 mol / L sodium hydroxide solution were added to the solution, and heated to reflux at 100°C for 6 hours. TLC monitors the reaction process; after the reaction, add 60mL ethyl acetate to the reactor reaction solution for extraction, then dry the extract phase with 20g of anhydrous sodium sulfate, filter to remove anhydrous sodium sulfate, and finally remove ethyl acetate by rotary evaporation at 35°C ester to give 5-methoxyindole-3-carbaldehyde as a red solid. The yield was 85% and the purity was 98.7%.

[0051] (2) Add 3g 5-methoxyindole-3-carbaldehyde, 50mL nitrometh...

Embodiment 2

[0056] (1) Add 6mL of phosphorus oxychloride and 40mL of DMF to the reactor, stir at 3°C ​​for 20min; dropwise add 12g of 5-methoxyindole mixed solution dissolved in 80mL of DMF solution, dropwise in 60min, drop When the addition time is controlled, the temperature is <10°C; after the dropwise addition, control the reactor at 30°C and stir for 2 hours, then add 45g of ice and 120mL of 5mol / L potassium hydroxide solution to the solution, and then heat and reflux at 90°C for 5h. TLC monitors the reaction process; after the reaction, add 200mL ethyl acetate to the reactor reaction solution for extraction, then dry the extract phase with 80g of anhydrous sodium sulfate, filter to remove anhydrous sodium sulfate, and finally remove ethyl acetate by rotary evaporation at 40°C ester to give 5-methoxyindole-3-carbaldehyde as a red solid. The yield was 86% and the purity was 98.5%.

[0057] (2) Add 6g 5-methoxyindole-3-formaldehyde, 100mL nitromethane and 6g ammonium carbonate to the ...

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 belongs to the technical field of medicine synthesis, and particularly relates to a preparation method of melatonin. According to the preparation method provided by the invention, 5-methoxy indole is taken as an original raw material, Vilsmeier-Haack formylation, a Henry reaction, a carbon-carbon double bond reduction reaction, a nitro reduction reaction and an acetylation reaction are sequentially performed, and the melatonin is finally prepared. The preparation method provided by the invention has the advantages of high product yield, cheap and easily available raw materials, mild reaction conditions, simple operation and low cost, and the prepared melatonin has high purity, has good economic benefits and is suitable for industrial production.

Description

technical field [0001] The invention belongs to the technical field of drug synthesis, and in particular relates to a preparation method of melatonin. Background technique [0002] Melatonin, also known as pineal gland, has a chemical name of N-acetyl-5-methoxytryptamine. It is a neurohormone mainly secreted by the pineal gland of mammals. It has various physiological functions such as circadian rhythm regulation and scavenging free radicals. It also has the health care effect of improving sleep. Some of its physiological and pharmacological activities have been applied to Pharmaceuticals and health food and other fields, the market prospect is broad. [0003] At present, there are many processes for preparing melatonin by chemical synthesis methods, mainly as follows: [0004] (1) Using 5-methoxyindole as a raw material, melatonin was prepared through four steps of oxalylation, amination, reduction, and acetylation. The method has few reaction steps, short cycle, simple ...

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): C07D209/14
CPCC07D209/14Y02P20/584
Inventor 汤须崇谢清萍赵应伟谢嘉斌
Owner BAYECAO HEALTH IND RES INST (XIAMEN) 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