Preparation method of 3,4-dimethoxy phenylpropionic acid

A technology of dimethoxyphenylpropionic acid and dimethoxybenzaldehyde is applied in the field of preparation of 3,4-dimethoxyphenylpropionic acid, a key intermediate of donepezil hydrochloride, and can solve unfavorable production and post-treatment, odor Odor and other problems, to achieve the effect of being conducive to recycling and applying, environment-friendly, and reducing pollution

Active Publication Date: 2016-05-25
山东诚汇双达药业有限公司
View PDF3 Cites 5 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Among them, pyridine and piperidine will be used as catalysts in the reaction process a, and the reaction an

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

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0028] Add 1200g of ethyl acetate to a 3L reaction flask, and add 166g of 3,4-dimethoxybenzaldehyde under stirring; after dissolving, add 640g of 15% sodium ethoxide ethanol solution dropwise at 15~20°C. After the dropwise addition, the solution was slowly warmed up at 50-55°C for 5 hours, and the reaction of the raw materials was monitored by TLC. The solution was cooled to 15-20°C and the pH value was adjusted to neutral with 150g of concentrated hydrochloric acid. Separation, the aqueous layer was extracted once with 100g ethyl acetate, the combined organic layer was washed once with saturated brine 300g; the organic phase was dried with sodium sulfate, filtered, concentrated and crystallized to obtain 212g of off-white 3,4-dimethoxy Ethyl cinnamate. The molar yield is 89.8%, and the liquid phase purity is over 98.5%.

[0029] Add 150g of 20% sodium hydroxide aqueous solution into the reaction flask, then add 118g of ethyl 3,4-dimethoxycinnamate, stir and mix, then heat up...

Embodiment 2

[0031] Add 1200g of ethyl acetate to a 3L reaction flask, and add 166g of 3,4-dimethoxybenzaldehyde under stirring; after dissolving, add 510g of 20% sodium ethoxide ethanol solution dropwise at 25~30°C. After the dropwise addition, the solution was slowly warmed up at 70-75°C for 2 hours, and the reaction of the raw materials was monitored by TLC. The solution was cooled to 20-25°C and the pH value was adjusted to neutral with 150g of concentrated hydrochloric acid. Separation, the aqueous layer was extracted once with 100g ethyl acetate, and the combined organic layer was washed once with 300g saturated brine; the organic phase was dried with sodium sulfate, filtered, concentrated and crystallized to obtain 215g of off-white 3,4-dimethoxy Ethyl cinnamate. The molar yield is 91.1%, and the liquid phase purity is over 98.5%.

[0032] Add 150g of 20% sodium hydroxide aqueous solution into the reaction flask, then add 118g of ethyl 3,4-dimethoxycinnamate, stir and mix, then hea...

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 chemical synthesis and in particular relates to a preparation method of a donepezil hydrochloride key intermediate 3,4-dimethoxy phenylpropionic acid. The method comprises the following steps: taking 3,4-dimethoxybenzaldehyde as a raw material to react with ethyl acetate under the action of sodium ethoxide to obtain an intermediate 3,4-dimethoxy ethyl cinnamate; hydrolyzing the 3,4-dimethoxy ethyl cinnamate under an alkaline condition, and carrying out hydrogenation reduction to obtain the 3,4-dimethoxy phenylpropionic acid. The preparation method provided by the invention has the advantages of environmental friendliness, high product purity, high yield and low raw material cost and the like.

Description

technical field [0001] The invention belongs to the technical field of chemical synthesis, and in particular relates to a preparation method of 3,4-dimethoxyphenylpropionic acid, a key intermediate of donepezil hydrochloride. Background technique [0002] Donepezil hydrochloride is a drug approved by the US FDA and the UK MCA for the symptomatic treatment of mild and moderate AD (Alzheimer's disease). The chemical name is 2,3-dihydroxy-5,6-dimethoxy -2-{1-(Benzyl)-4-piperidinylmethyl}-1H-inden-1-one hydrochloride. AD is a kind of acquired mental decline with memory loss as the main manifestation, accompanied by other cognitive impairment. Donepezil hydrochloride is a second-generation cholinesterase inhibitor. Its therapeutic effect is to reversibly inhibit the hydrolysis of acetylcholine caused by acetylcholinesterase and increase the content of acetylcholine at the receptor site. [0003] 3,4-dimethoxyphenylpropionic acid is the key intermediate of donepezil hydrochlorid...

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): C07C51/36C07C59/64
CPCC07C51/09C07C51/36C07C67/343C07C69/734C07C59/64
Inventor 李跃东刘志文宋希军孙宝亮薛智龙
Owner 山东诚汇双达药业有限公司
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