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

Method for preparing methyldopa by directly hydrolyzing 5-methyl-5-(3,4-dimethoxybenzyl)hydantoin with acid

A technology of dimethoxybenzyl and methyldopa is applied in chemical instruments and methods, preparation of cyanide reactions, preparation of organic compounds, etc., and can solve problems such as purity, yield decline, and increase in by-products.

Active Publication Date: 2013-02-06
ZHEJIANG CHIRAL MEDICINE CHEM
View PDF4 Cites 1 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In the hydantoin method, an important disadvantage of hydrolyzing hydantoin with BaOH is that the hydrolyzed product needs to be mixed with sulfuric acid and DL-α-methyl-(3,4-dimethoxyphenyl)-α-amino Barium propionate undergoes an exchange reaction, and then undergoes complicated post-treatment of the intermediate product to remove the barium sulfate generated to obtain DL-α-methyl-(3,4-dimethoxyphenyl)-α-aminopropyl acid, and, in the hydrobromic acid further high-temperature hydrolysis demethylation stage, the oxidative properties of residual sulfuric acid make the polyphenol-like structure after demethylation produce a variety of chemical reactions under high temperature and oxidation conditions, and the structure of some compounds Unknown changes increase by-products and decrease purity and 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
  • Method for preparing methyldopa by directly hydrolyzing 5-methyl-5-(3,4-dimethoxybenzyl)hydantoin with acid
  • Method for preparing methyldopa by directly hydrolyzing 5-methyl-5-(3,4-dimethoxybenzyl)hydantoin with acid

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0038] In a three-necked flask equipped with a thermometer, a stirrer and a reflux condenser, add 4.3 g (0.016 mol) of 5-methyl-5-(3,4-dimethoxybenzyl) hydantoin and add 36% 24.3 g (0.24 mol) of concentrated hydrochloric acid, then slowly heated in an oil bath to 65-70°C (40 minutes), stirred and reacted for 6 hours, then heated to 100-110°C (reaching vigorous reflux), stirred and reacted for 24 hours. After the reaction was completed, N was directly introduced into the reaction mixture slowly. 2 , while extracting excess HCl by distillation under reduced pressure. Adjust the pH of the solution with ammonia water and solids appear, stir until the pH is constant. Then, carefully adjust the pH to 6, let stand for 1 hour, and filter the solid. The solid was washed with 4×25ml of acetone to obtain a white solid. It was then vacuum dried at 50°C for 5 hours. Obtain product DL-2-amino-3-(3,4-dihydroxyphenyl)-2-methyl-propionic acid (C 10 h 13 NO 4 ·H 2 o 1.5 ) namely methyl...

Embodiment 2

[0041]In a three-necked flask equipped with a thermometer, a stirrer and a reflux condenser, add 4.3g (0.016mol) of 5-methyl-5-(3,4-dimethoxybenzyl)hydantoin, add 47% 41.4 g (0.24 mol) of hydrobromic acid, then slowly heated in an oil bath to 65-70°C (40 minutes), stirred and reacted for 6 hours, then heated to 100-120°C (reaching vigorous reflux), stirred and reacted for 18 hours. After the reaction was completed, N was directly introduced into the reaction mixture slowly. 2 , while extracting excess hydrobromic acid by distillation under reduced pressure. Adjust the pH of the solution with ammonia water and solids appear, stir until the pH is constant. Then, carefully adjust the pH to 6, let stand for 1 hour, and filter the solid. The solid was washed with 4×25ml of acetone to obtain a white solid. It was then vacuum dried at 50°C for 5 hours. Obtain product DL-2-amino-3-(3,4-dihydroxyphenyl)-2-methyl-propionic acid (C 10 h 13 NO 4 ·H 2 o 1.5 ) That is 3.63 grams of...

Embodiment 3

[0044] In a three-necked flask equipped with a thermometer, a stirrer and a reflux condenser, add 4.3g (0.016mol) of 5-methyl-5-(3,4-dimethoxybenzyl)hydantoin, add 47% 20.7 g (0.12 mol) of hydrobromic acid. Then the oil bath was slowly heated to 65-70°C (40 minutes), stirred and reacted for 6 hours, then heated to 100-120°C (to achieve vigorous reflux), stirred and reacted for 24 hours. After the reaction was completed, N was directly introduced into the reaction mixture slowly. 2 , while extracting excess hydrobromic acid by distillation under reduced pressure. Adjust the pH of the solution with ammonia water and solids appear, stir until the pH is constant. Then, carefully adjust the pH to 6, let stand for 1 hour, and filter the solid. The solid was washed with 4×25ml of acetone to obtain a white solid. It was then vacuum dried at 50°C for 5 hours. Obtain product DL-2-amino-3-(3,4-dihydroxyphenyl)-2-methyl-propionic acid (C 10 h 13 NO 4 ·H 2 o 1.5 ) that is methyld...

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 one of key steps of chemical synthesis of medicine methyldopa [alpha-methyl-(3,4-dihydroxyphenyl]-alpha-alanine] or synthesis of chiral medicine L-methyldopa [L-alpha-methyl-(3,4-dihydroxyphenyl]-alpha-alanine]: reaction for preparing methyldopa by hydrolyzing 5-methyl-5-(3,4-dimethoxybenzyl)hydantoin. The invention relates to a method for preparing methyldopa or L-methyldopa by directly hydrolyzing 5-methyl-5-(3,4-dimethoxybenzyl)hydantoin with acid at appropriate temperature. When disacidification is carried out under reduced pressure after the reaction finishes, N2 is introduced to protect the product from easy oxidative stain and accelerate the disacidification. In order to protect the product from deterioration, the vacuum drying temperature of the product is generally carried out at 50 DEG C for 5 hours.

Description

[0001] Technical field [0002] The technology field of the present invention belongs to chemical synthetic drugs, methaldopa, α-methyl-(3,4-dihydroxylphenyl)-α-amino propyate, the same] or synthetic handicapyOne of the key steps in the key steps of Bazi [L-METHYLDOPA, L-α-methyl-(3,4-dihydroxylphenyl)-α-aminopropine, below]: Hydrolysis 5-methyl-5- (3 3, 4-dimer oxygen-based radius) The reaction of nailopopico is prepared for nailoba. [0003] Background technique [0004] L-methylopopharba is a catecinol hormone in the biological body. It is a decarcase inhibitor.2): 1012103.], has the effect of anti -hypertension, clinically used to treat hypertension [xu j M, Zheng H J. Clinical Application and Evaluation of Methyldopa [J].), 1990, 9 (6): 367-369.].L-methyldaba is also one of the main drugs for treating Parkinson's disease [Bronstein, J. M., StereotActic Pallidotomy in the Treatment of Parkinson Disease, Archivers of Neurology, (1999) .56,1064-1069.]. [0005] Synthetic methyl...

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): C07C229/36C07C227/24
Inventor 徐伟亮汪静徐子河黄有明
Owner ZHEJIANG CHIRAL MEDICINE CHEM
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