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Method for synthesizing 2-methoxy-4-amino-5-ethylsulfonyl benzoic acid

A technology of ethylsulfone benzoic acid and methyl acetaminobenzoate, which is applied in the field of preparation of pharmaceutical intermediates, can solve problems such as low yield, long process route, and poor product quality, and achieve high product yield and process route Simple, good product quality effect

Active Publication Date: 2015-07-08
苏州诚和医药化学有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] The purpose of the invention is to provide a new synthetic method of 2-methoxy-4-amino-5-ethylsulfone-benzoic acid for the disadvantages of long operational route, low yield and poor product quality in the prior art

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0024] Slowly add 150g (0.67mol) of methyl 2-methoxy-4-acetamidobenzoate into a 1000mL four-necked reaction flask containing 391g (3.36mol) of chlorosulfonic acid below 10°C with a chlorination absorption system, and add The process is controlled below 10°C, after the feeding is completed, the reaction is carried out at 5-10°C for 5 hours. After the reaction was completed, the reaction solution was poured into 1000 ml of ice water, solids were precipitated, and suction filtration gave 220.6 g of a wet product of methyl 2-methoxy-4-acetylamino-5-sulfonyl chloride benzoate, with a water content of 12.4%. The dry product is 193.2g (0.60mol), and the molar yield is 89.6%. Add the wet product of methyl 2-methoxy-4-acetylamino-5-sulfonyl chloride benzoate in batches to 2000 ml of 800 mL aqueous solution containing 302.5 g (2.4 mol) of sodium sulfite at 75-80 °C with a reflux condenser In the four-necked reaction flask, keep warm for 1 hour after feeding. Then cool to 35-40°C, and ...

Embodiment 2

[0026] Slowly add 100.5g (0.45mol) of methyl 2-methoxy-4-acetamidobenzoate into a 1000mL four-necked reaction flask containing 262g (2.25mol) of chlorosulfonic acid with a chlorination absorption system below 10°C, The feeding process is controlled below 10°C. After the feeding is completed, the reaction is carried out at 5-10°C for 8 hours. After the reaction was completed, the reaction solution was poured into 800 ml of ice water, solids were precipitated, and suction filtration gave 144.6 g of a wet product of methyl 2-methoxy-4-acetylamino-5-sulfonylchloride benzoate, a water content of 13.2%. The dry product was 125.5g (0.39mol), and the molar yield was 86.4%. Add the wet product of methyl 2-methoxy-4-acetylamino-5-sulfonylchloride benzoate in batches to 2000 ml of 600 mL aqueous solution containing 245.8 g (1.95 mol) of sodium sulfite at 75 to 80 ° C with a reflux condenser In the four-necked reaction flask, keep warm for 1 hour after feeding. Then cool to 35-40°C, and...

Embodiment 3

[0028] Slowly add 201g (0.9mol) of methyl 2-methoxy-4-acetamidobenzoate into a 1000mL four-necked reaction flask containing 839g (7.2mol) of chlorosulfonic acid below 10°C and equipped with a chlorination absorption system. The process is controlled below 10°C, after the feeding is completed, the reaction is carried out at 5-10°C for 6 hours. After the reaction was completed, the reaction solution was poured into 1500 ml of ice water, solids were precipitated, and suction filtration gave 277 g of a wet product of methyl 2-methoxy-4-acetylamino-5-sulfonyl chloride benzoate, with a water content of 10.6%. The product was 247.7g (0.77mol), and the molar yield was 85.6%. Add the wet product of methyl 2-methoxy-4-acetamido-5-sulfonylchloride benzoate in batches to 2000 ml four- In a reaction bottle, keep the temperature for 1 hour after the addition. Then cool to 35-40°C, and slowly add 355.7 g (2.3 mol) of diethyl sulfate dropwise at this temperature. After the dropwise addition...

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Abstract

The invention discloses a method for synthesizing a 2-methoxy-4-amino-5-ethylsulfonyl benzoic acid. The method comprises the following steps of: reacting 2-methoxy-4-acetamido methyl benzoate with chlorosulfonic acid for 5-10 hours according to a mole ratio of 1:(5-8), subsequently carrying out hydrolysis separation so as to obtain 2-methoxy-4-acetamido-5-sulfonyl chloride methyl benzoate, furthermore reacting the obtained 2-methoxy-4-acetamido-5-sulfonyl chloride methyl benzoate with sodium sulfite and diethyl sulfate for 5-10 hours according to a mole ratio of 1:(4-6):(2-3) under the backflow condition, and finally carrying out hydrochloric acid acidification and the like so as to obtain the objective product, namely, the 2-methoxy-4-amino-5-ethylsulfonyl benzoic acid. The method disclosed by the invention is simple in process route, high in product yield and good in product quality, the total yield can be 75%, the purity can be 99.5%, and the product is white; the method solves the defects that in the conventional process, the synthesis route is long, the yield is low, the product quality is poor and the like, thereby being more applicable to industrial production requirements; a novel method for synthesizing the 2-methoxy-4-amino-5-ethylsulfonyl benzoic acid is provided.

Description

technical field [0001] The present invention relates to the preparation technology of medicine intermediate, specifically, a kind of synthesis method of 2-methoxy-4-amino-5-ethylsulfonylbenzoic acid. Background technique [0002] 2-Methoxy-4-amino-5-ethylsulfonylbenzoic acid, also known as 4-amino-5-(ethylsulfonyl)-2-methoxybenzoic acid, amic acid or 2-methoxy -4-Amino-5-ethanesulfonylbenzoic acid, molecular formula: C 10 h 13 NO 5 S, molecular weight: 259.28, it is an important intermediate for the synthesis of antipsychotic drug amisulpride. [0003] There are many reports about the synthetic route of 2-methoxyl-4-amino-5-ethylsulfone benzoic acid, and the main routes used in industrialized production are: [0004] , [0005] The route is to obtain the target product (6) through deacetylation, thiocyanation, ethylation, oxidation, and alkaline hydrolysis of methyl 2-methoxy-4-acetamidobenzoate (1). After 5 steps of reaction, However, the yields of each step are low...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07C317/48C07C315/04
Inventor 王利明夏秋景陈洁
Owner 苏州诚和医药化学有限公司