Synthesis of Important intermediate for mosapride citrate

A technology for the preparation of mosapride citrate, which is applied in the field of medicine, can solve the problems affecting the popularization and application of mosapride citrate, the detection is difficult to meet the requirements, and the quality of intermediates is poor, so as to improve the synthesis yield. rate and the quality of finished products, the effect of smooth response and the alleviation of price problems

Inactive Publication Date: 2005-11-09
LUNAN BETTER PHARMA
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AI Technical Summary

Problems solved by technology

[0003] There are many deficiencies in the existing mosapride citrate raw material synthesis process, mainly in the process of preparing intermediate (1) 2-ethoxyl-4-acetamido-5-chlorobenzoic acid, ethylating reagent iodine Ethane is expensive and the yield is not high, causing the preparation cost of intermediate (1) to be close to half of the total cost of mosapride citrate raw material synthesis; intermediate (2) 4-(4-fluorobenzyl)- The synthesis yield of 2-aminomethylmorpholine is also low, only 40%, and the finished product has poor color, which is dark brown
After reverse purification of the intermediate, it was found that it was the poor quality of the intermediate (2) that caused the final product to often fail to meet the requirements when detecting related substances
Many factors have affected the popularization and application of mosapride citrate

Method used

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  • Synthesis of Important intermediate for mosapride citrate
  • Synthesis of Important intermediate for mosapride citrate
  • Synthesis of Important intermediate for mosapride citrate

Examples

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Effect test

example 1

[0016] Preparation of the intermediate o-hydroxyp-aminobenzoic acid: 100 g of sodium o-hydroxyp-aminobenzoate dihydrate was dissolved in water, stirred, and concentrated hydrochloric acid was added dropwise to 150 g, cooled and filtered to obtain the intermediate o-hydroxyp-aminobenzoic acid, The yield was 96.5%.

[0017]

example 2

[0019] Preparation of intermediate o-hydroxy p-aminobenzoic acid methyl ester: intermediate o-hydroxy p-aminobenzoic acid was dissolved in methanol, stirred, concentrated sulfuric acid was added dropwise, refluxed, methanol was removed, and saturated K 2 CO 3 solution. Cool, stand still, and filter to obtain an off-white solid, which is methyl o-hydroxy p-aminobenzoate, with a yield of 79.7%.

[0020]

example 3

[0022] Preparation of the intermediate o-hydroxy p-acetamidobenzoic acid methyl ester: the intermediate o-hydroxy p-aminobenzoic acid methyl ester is dissolved in glacial acetic acid, stirred, acetic anhydride is added dropwise, and then the solvent is removed, NaOH solution is added to the raffinate, and the The white solid was filtered to obtain the intermediate methyl o-hydroxy p-aminobenzoate with a yield of 80.0%.

[0023]

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Abstract

The present invention relates to the preparation process of important intermediates for Mosapride citrate, 2-oxethyl-4-actamino-5-chlorobenzoic acid and 4-(4-fluorobenzyl-2- aminomethyl morpholine. The intermediate 2-oxethyl-4-actamino-5-chlorobenzoic acid is prepared with amino salicylic acid as initial material and through acidification with hydrochloric acid, esterification with methol, acetylation with acetic anhydride, ethylation, NCS chlorination and alkali hydrolysis. The intermediate 4-(4-fluorobenzyl-2- aminomethyl morpholine is prepared with p-fluorobenzaldehyde and phthalimide as initial material and through dropping at 70-90 deg.c, maintaining at 125-145 deg.c, and post-treatment in ice bath in 2-10 deg.c while adding acetic anhydride through stirring for 10-20hr. The present invention can raise the yield of Mosapride citrate and lower its production cost.

Description

technical field [0001] The invention provides a preparation method of mosapride citrate, which belongs to the technical field of medicine. Background technique [0002] With the acceleration of the pace of social life, the improvement of people's living standards and the change of diet structure and other factors, the number of patients with low gastric motility is increasing, and people's quality of life is greatly affected. Mosapride citrate, as the first gastric motility drug without dopamine receptor antagonism, has been widely used at home and abroad because of its good clinical efficacy, low side effects, safety, and high efficiency. , Restoring health provides new options and assistance. [0003] There are many deficiencies in the existing mosapride citrate raw material synthesis process, mainly in the process of preparing intermediate (1) 2-ethoxy-4-acetamido-5-chlorobenzoic acid, ethylating reagent iodine Ethane is expensive and the yield is not high, causing the ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07C231/10C07C233/54C07D241/04C07D265/30
Inventor 赵志全
Owner LUNAN BETTER PHARMA
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