Preparation method of methyl 4-acetamido-5-chloro-2-methoxybenzoate

A technology of methyl methoxybenzoate and acetamide, which is applied in the field of chemical synthesis, can solve the problems of large environmental pollution, unfavorable industrial production, and strong smell of acetic acid, and achieve the goals of saving transportation, saving raw material costs, and reducing waste solvents the effect produced

Inactive Publication Date: 2016-04-27
JINAN CHENGHUI SHUANGDA CHEM
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Since chlorine gas is a highly toxic gas, it has high requirements in terms of transportation, storage, and production equipment, and there are risks in the transportation and production process, and the smell of acetic acid is relatively large, and a large amount of industrial waste acid is produced in the post-treatment process. Great environmental pollution, not conducive to industrial production

Method used

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  • Preparation method of methyl 4-acetamido-5-chloro-2-methoxybenzoate

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0030] Add 100g of N,N-dimethylformamide into a 1L reaction flask, add 50g of methyl 4-acetamido-2-methoxybenzoate, stir to dissolve, add 33g of N-chlorosuccinimide, slowly Raise the temperature to 35°C, keep the heat for 5 hours, then raise the temperature to 65°C, and hold the heat for 4 hours; after the reaction is completed, cool down to 0°C to crystallize for 8 hours, and shake off the material to obtain 4-acetamido-5-chloro-2-methoxybenzoic acid The crude methyl ester wet product and the N,N-dimethylformamide mother liquor are reserved for later use; the crude 4-acetamido-5-chloro-2-methoxybenzoic acid methyl ester wet product is added to 100g of deionized water, and the temperature is raised Heat at 50°C for 3h, cool down to 5°C, filter with suction, and dry to obtain 43g of off-white methyl 4-acetamido-5-chloro-2-methoxybenzoate, with a molar yield of 74.5% and an HPLC purity of ≥99.8% .

Embodiment 2

[0032] Add 150g of N,N-dimethylformamide into a 1L reaction flask, add 50g of methyl 4-acetamido-2-methoxybenzoate, stir to dissolve, add 50g of N-chlorosuccinimide, slowly Raise the temperature to 40°C, hold the reaction for 4 hours, then raise the temperature to 80°C, hold the reaction for 3 hours; after the reaction is completed, cool down to 0°C, hold the heat for 8 hours, and shake off the material to obtain 4-acetamido-5-chloro-2-methoxybenzene Methyl formate crude wet product, N,N-dimethylformamide mother liquor reserved for future use; 4-acetamido-5-chloro-2-methoxymethyl benzoic acid crude wet product was added to 100g deionized water, Heat up to 50°C for 4 hours, cool down to 5°C, filter with suction, and dry to obtain 47.5g of off-white methyl 4-acetamido-5-chloro-2-methoxybenzoate, with a molar yield of 82.7%, HPLC purity≥ 99.8%.

Embodiment 3

[0034] Add 50g of N,N-dimethylformamide into a 1L reaction flask, add 50g of methyl 4-acetamido-2-methoxybenzoate, stir to dissolve, add 25g of N-chlorosuccinimide, slowly Raise the temperature to 45°C, heat-retain for 4 hours, then raise the temperature to 60°C, heat-retain for 5 hours; after the reaction is completed, cool down to 0°C, heat-preserve and crystallize for 8 hours, and shake off the material to obtain 4-acetamido-5-chloro-2-methoxybenzene Methyl formate crude wet product, N,N-dimethylformamide mother liquor reserved for future use; 4-acetamido-5-chloro-2-methoxymethyl benzoic acid crude wet product was added to 100g deionized water, Heat up to 50°C for 3 hours, cool down to 5°C, filter with suction, and dry to obtain 45.1 g of off-white methyl 4-acetamido-5-chloro-2-methoxybenzoate, with a molar yield of 78.2%, HPLC purity ≥ 99.8%.

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Abstract

The invention relates to the technical field of chemical synthesis, and concretely relates to a preparation method of methyl 4-acetamido-5-chloro-2-methoxybenzoate. The method comprises the following steps: dissolving methyl 4-acetamido-2-methoxybenzoate in N,N-dimethyl formamide, adding N-chlorosuccimide, carrying out a heat insulation reaction to obtain crude methyl 4-acetamido-5-chloro-2-methoxybenzoate, separating out the crude methyl 4-acetamido-5-chloro-2-methoxybenzoate to obtain an N,N-dimethyl formamide mother liquor, and directly using the N,N-dimethyl formamide mother liquor as a solvent for preparing methyl 4-acetamido-5-chloro-2-methoxybenzoate without treatment. The preparation method has the advantages of high mole yield, low cost, safety and environmental protection.

Description

technical field [0001] The invention relates to the technical field of chemical synthesis, in particular to a method for preparing a metoclopramide intermediate 4-acetamido-5-chloro-2-methoxybenzoic acid methyl ester. Background technique [0002] Metoclopramide, also known as metoclopramide, is a dopamine D2 receptor antagonist, and also has 5-hydroxytryptamine 4 (5-HT4) receptor agonistic effect, and has a slight inhibitory effect on 5-HT3 receptors effect. It can act on dopamine receptors in the medullary emetic chemoreceptor zone (CTZ) to increase the threshold of CTZ, and has a strong central antiemetic effect. [0003] Methyl 4-acetamido-5-chloro-2-methoxybenzoate is a key intermediate in the synthesis of metoclopramide. For its synthesis, there are few publicly reported literatures in China. The structural formula of methyl 4-acetamido-5-chloro-2-methoxybenzoate is as follows: [0004] . [0005] 文献MMurakami,NInukai,AKoda,KNakano,“AnImprovedSynthesisofMetoclopr...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07C231/12C07C233/54
CPCC07C231/12C07C233/54
Inventor 王文新李跃东曹晓华刘学文王永广
Owner JINAN CHENGHUI SHUANGDA CHEM
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