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Method for preparing 5-amino benzofuran carboxylic ester

A technology for aniline diazonium compound, which is applied in the field of preparation of 5-aminobenzofuran carboxylate, can solve the problems such as being unsuitable for mass production, large amount of DBU, difficult to purify intermediate target and the like

Active Publication Date: 2009-12-23
EAST CHINA UNIV OF SCI & TECH +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] (1) The selectivity of the salicylaldehyde nitration reaction is poor (while generating the intermediate target 5-nitrosalicylaldehyde, the by-product 3-nitrosalicylaldehyde is inevitably generated), and the intermediate target is difficult to purify (Need a large amount of solvent, after repeated crystallization to separate 5-nitrosalicylaldehyde and 3-nitrosalicylaldehyde)
[0008] (2) When 5-nitrosalicylaldehyde and alkyl haloacetate are subjected to ring-closure reaction after etherification, the hydrolysis of ester group needs to be suppressed. The existing method is: use sodium alkoxide (sodium methylate or sodium ethylate ) is a catalyst for the ring-closing reaction, although it can achieve the purpose of inhibiting the hydrolysis of ester groups, but it needs to add a step of dehydration reaction, and requires a special acidic dehydration catalyst (Yoo, S.-E.; Lee, S.-H.; Kim, S .-K.; Lee, S.-H.Bioorg.Med.Chem.1997, 5, 445), making the reaction cumbersome
Patel etc. have reported using 1,8-diazacyclo[5,4,0]undecene-7 (abbreviated as DBU) to obtain ester-containing benzofuran compound (Patel, V.F.; Andis, S.L.; Enkema, J.K.; Johnson, D.A.; Kennedy, J.H.; Mohamadi, F.; Schultz, R.M.; Sooze, D.J.; , and the amount of DBU is large, the cost is also high, not suitable for mass production

Method used

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  • Method for preparing 5-amino benzofuran carboxylic ester
  • Method for preparing 5-amino benzofuran carboxylic ester
  • Method for preparing 5-amino benzofuran carboxylic ester

Examples

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Embodiment 1

[0032] Diazotization of Aniline and Coupling with Salicylaldehyde

[0033] Add 50mL of water, 37.5mL (0.45mol) of concentrated hydrochloric acid and 14g (0.15mol) of aniline into a 400mL beaker, and then add 150g of ice. Under stirring, add dropwise 30% sodium nitrite solution (10.8g sodium nitrite dissolved in 26mL water) into the aniline within 15-20min at 0-5°C. After dropping, the solution pH<3 (starch potassium iodide test paper appears blue). React at 0-5°C for 30 minutes, filter to obtain bright yellow and clear diazonium liquid.

[0034] Dissolve 18.3g (0.15mol) of salicylaldehyde in a solution prepared by 12g of sodium hydroxide and 600mL of water, then adjust the pH to 9 with hydrochloric acid, add 500g of crushed ice, add diazo solution dropwise within 40 to 60 minutes at 0-5°C, Simultaneously adjust the pH to about 8 with 10% sodium hydroxide solution, continue the reaction for 3h, adjust the pH to about 5 with hydrochloric acid after stopping the reaction, stir f...

Embodiment 2

[0043] Diazotization of Aniline and Coupling with Salicylaldehyde

[0044] Add 50mL of water, 37.5mL (0.45mol) of concentrated hydrochloric acid and 14g (0.15mol) of aniline into a 400mL beaker, and then add 150g of ice. Under stirring, add dropwise 30% sodium nitrite solution (10.8g sodium nitrite dissolved in 26mL water) into the aniline within 15-20min at 0-5°C. After dropping, the solution pH<3 (starch potassium iodide test paper appears blue). React at 0-5°C for 30 minutes, filter to obtain bright yellow and clear diazonium liquid.

[0045] Dissolve 19.2g (0.157mol) of salicylaldehyde in a solution prepared by 12g of sodium hydroxide and 600mL of water, then adjust the pH to 9 with hydrochloric acid, add 500g of crushed ice, add diazo solution dropwise within 40 to 60 minutes at 0-5°C, Simultaneously adjust the pH to about 8 with 10% sodium hydroxide solution, continue the reaction for 3 h, adjust the pH to about 5 with hydrochloric acid after stopping the reaction, stir...

Embodiment 3

[0054] Diazotization of Aniline and Coupling with Salicylaldehyde

[0055] Add 50mL of water, 37.5mL (0.45mol) of concentrated hydrochloric acid and 14g (0.15mol) of aniline into a 400mL beaker, and then add 150g of ice. Under stirring, add dropwise 30% sodium nitrite solution (10.8g sodium nitrite dissolved in 26mL water) into the aniline within 15-20min at 0-5°C. After dropping, the solution pH<3 (starch potassium iodide test paper appears blue). React at 0-5°C for 30 minutes, filter to obtain bright yellow and clear diazonium liquid.

[0056] Dissolve 18.3g (0.15mol) of salicylaldehyde in a solution prepared by 12g of sodium hydroxide and 600mL of water, then adjust the pH to 9 with hydrochloric acid, add 500g of crushed ice, add diazo solution dropwise within 40 to 60 minutes at 0-5°C, Simultaneously adjust the pH to about 8.5 with 10% sodium hydroxide solution, continue the reaction for 3h, adjust the pH to about 5 with hydrochloric acid after stopping the reaction, stir...

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Abstract

The invention relates to a method for preparing 5-amino benzofuran-2-carboxylic ester, which comprises following steps: obtaining an intermediate from the reaction of salicylaldehyde and aniline diazonium salt; and obtaining the target by processing the obtained intermediate and halogenated acetic acid alkyl ester consequentially with etherification reaction, ring-closing reaction and reduction reaction. The invention provides the method for preparing 5-amino benzofuran-2-carboxylic ester, which has the advantages of high reaction selectivity and simple operation; in addition, the method is suitable for scaled commercial preparation.

Description

technical field [0001] The invention relates to a preparation method of 5-aminobenzofuran carboxylate, in particular to a preparation method of 5-aminobenzofuran-2-carboxylate. Background technique [0002] 5-Aminobenzofuran-2-carboxylate (its structure is shown in formula 1) is a class of biologically active compounds (such as its effect on 5-HT 1a - antagonism and inhibition of 5-HT reuptake, which affects serotonergic transmission, inhibits serotonin reuptake, etc.), has wide applications in the pharmaceutical field. [0003] [0004] The existing method for preparing 5-aminobenzofuran-2-carboxylates is mainly: salicylaldehyde is the starting material, followed by nitration reaction, etherification with alkyl haloacetate and ring-closing reaction and adding It is prepared after hydrogen reduction reaction, and its synthetic route is as follows: [0005] [0006] The main defective that above-mentioned prior art exists is: [0007] (1) The selectivity of the salic...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D307/85
Inventor 沈永嘉王成云黄鹏过介生陶建伟周长凯左虎进温雪俊
Owner EAST CHINA UNIV OF SCI & TECH