Preparation method of 2,5-dimethoxyphenylacetic acid

A technology of dimethoxybenzene and dimethoxybenzaldehyde, applied in the field of drug synthesis, can solve the problems of good safety, difficulty in meeting market demands and high cost, and achieve the effect of being beneficial to environmental protection

Pending Publication Date: 2021-02-05
ASTATECH CHENGDU BIOPHARM CORP
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Among them, drug therapy still plays a major role in clinical practice. Clinical studies have found that feretin has a positive effect on the treatment of PD, and at the same time has low toxicity and good safety. However, 2,5-dimethoxyphenylacetic acid is required in the synthesis of feredin As a starting material, a series of aryl acetic acid compounds are synthesized by the Willgerodt-Kindler method in the current report, and 2,5-dimethoxyphenylacetic acid is prepared by this method. The yield is low and the cost is high, so it is difficult to satisfy the market need

Method used

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  • Preparation method of 2,5-dimethoxyphenylacetic acid
  • Preparation method of 2,5-dimethoxyphenylacetic acid
  • Preparation method of 2,5-dimethoxyphenylacetic acid

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0025]

[0026] A. Add 13.82g (0.1mol) of 1,4-dimethoxybenzene and 200mL of anhydrous dichloromethane to a 500mL three-necked round-bottomed flask. 0.12mol) of anhydrous dichloromethane solution 45mL, dropwise added 90mL of anhydrous dichloromethane solution dissolved in 1,1-dichloromethyl ether (16.09g, 0.14mol), added dropwise for 1.5h, and stirred at room temperature for 30min , add 300g ice cubes, 8mL concentrated hydrochloric acid to the reaction solution, stir for 1h, separate the liquids, extract the aqueous phase with dichloromethane twice, 100mL each time, combine the organic phases, wash the organic phase twice with water, 100mL each time, anhydrous Dry over sodium sulfate and concentrate under reduced pressure to obtain 16.57 g of oily product 2,5-dimethoxybenzaldehyde, yield 98%, HPLC 97.9%;

[0027] B. Add 10g (0.060mol) of 2,5-dimethoxybenzaldehyde and 80mL of methanol to a 500mL three-neck round bottom flask, cool down to 0°C, and add NaBH in batches 4 2.05g...

Embodiment 2

[0033]

[0034] A. Add 13.82g (0.1mol) of 1,4-dimethoxybenzene and 200mL of anhydrous dichloromethane into a 500mL three-necked round-bottomed flask. , 0.12mol) of anhydrous dichloromethane solution 45mL, dropwise added 90mL of anhydrous dichloromethane solution dissolved in 1,1-dichloromethyl ether (14.94g, 0.13mol), added dropwise for 1h, and stirred at room temperature for 30min , add 300g of ice cubes, 8mL of concentrated hydrochloric acid to the reaction solution, stir for 2h, separate the liquids, extract the aqueous phase with dichloromethane twice, 100mL each time, combine the organic phases, wash the organic phase with water twice, 100mL each time, anhydrous Dry over sodium sulfate and concentrate under reduced pressure to obtain 16.22 g of oily product 2,5-dimethoxybenzaldehyde, yield 97.6%, HPLC 97.9%;

[0035] B. Add 10g (0.060mol) of 2,5-dimethoxybenzaldehyde and 80mL of methanol to a 500mL three-neck round bottom flask, cool down to -10°C, and add NaBH in batc...

Embodiment 3

[0041]

[0042] A. Add 13.82g (0.1mol) of 1,4-dimethoxybenzene and 200mL of anhydrous dichloromethane into a 500mL three-necked round-bottomed flask. 0.12mol) of anhydrous dichloromethane solution 45mL, dropwise added 90mL of anhydrous dichloromethane solution dissolved in 1,1-dichloromethyl ether (17.2g, 0.15mol), added dropwise for 3h, and stirred at room temperature for 30min. Add 300g of ice cubes and 8mL of concentrated hydrochloric acid to the reaction solution, stir for 2h, separate the liquids, extract the aqueous phase with dichloromethane twice, 100mL each time, combine the organic phases, wash the organic phase with water twice, 100mL each time, anhydrous sulfuric acid Dry over sodium and concentrate under reduced pressure to obtain 16.31 g of oily product 2,5-dimethoxybenzaldehyde, yield 98.2%, HPLC 97.9%;

[0043] B. Add 10g (0.060mol) of 2,5-dimethoxybenzaldehyde and 80mL of methanol to a 500mL three-necked round-bottomed flask, cool down to 10°C, and add NaBH...

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Abstract

The invention belongs to the technical field of drug synthesis, and particularly relates to a preparation method of 2,5-dimethoxyphenylacetic acid, wherein the method comprises the following steps: A,reacting 1,4-dimethoxybenzene in a formylation system to obtain 2,5-dimethoxybenzaldehyde; B, reacting the 2,5-dimethoxybenzaldehyde obtained in the step A with a reducing agent, extracting a reaction system, then combining organic phases, drying, concentrating under reduced pressure and distilling a crude product to obtain 2,5-dimethoxybenzyl alcohol; C, reacting the 2,5-dimethoxybenzyl alcoholobtained in the step B with a bromination reagent to obtain 2-bromomethyl-1,4-dimethoxybenzene; and D, reacting the 2-bromomethyl-1,4-dimethoxybenzene obtained in the step C with magnesium or butyl lithium and carbon dioxide in a solvent to obtain the 2,5-dimethoxyphenylacetic acid. The yield and the total yield of the 2,5-dimethoxyphenylacetic acid obtained by the method disclosed by the invention are both higher than those of 2,5-dimethoxyphenylacetic acid synthesized by a Willegerdt-Kindler method.

Description

technical field [0001] The invention belongs to the technical field of medicine synthesis, and in particular relates to a preparation method of 2,5-dimethoxyphenylacetic acid. Background technique [0002] Parkinson's disease (Parkinson's disease, PD) is a common neurodegenerative disease, the main clinical symptoms are muscle tremors, stiffness, movement difficulties, body posture and motor balance disorders. Further development will also appear recognition, perception, memory impairment and obvious dementia. [0003] The main pathological feature of PD is the degeneration of dopaminergic neurons in the substantia nigra compacta, and the content of dopaminergic neurotransmitters in the striatum is significantly reduced. The cause of dopaminergic neuron degeneration is unknown so far. Genetics, infection, abnormal immune function, aging, and neurotoxins in vivo and in vitro all play a role in the pathogenesis of PD. Oxidative stress and mitochondrial dysfunction play a role...

Claims

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Application Information

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IPC IPC(8): C07C51/15C07C59/64C07C41/22C07C43/225C07C41/26C07C43/23C07C45/00C07C47/575
CPCC07C51/15C07C41/22C07C41/26C07C45/00C07C47/575C07C43/23C07C43/225C07C59/64
Inventor 杜全海杜乐高塔姆杜帕蒂周强黄秀君郭鹏
Owner ASTATECH CHENGDU BIOPHARM CORP
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