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Environmentally friendly method for preparing 4,6-dihalogen-substituted indole-2-ethyl formate

A technology of ethyl formate and dihalogen, applied in environmentally friendly preparation 4, can solve problems such as a large amount of waste water, large amount of polyphosphoric acid, environmental pollution, etc., and achieve the effect of cost reduction

Pending Publication Date: 2018-10-23
INST OF MATERIA MEDICA AN INST OF THE CHINESE ACAD OF MEDICAL SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The amount of polyphosphoric acid used in this route is large, and a large amount of waste water is also generated, causing serious pollution to the environment, and the post-treatment operation is cumbersome.

Method used

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  • Environmentally friendly method for preparing 4,6-dihalogen-substituted indole-2-ethyl formate
  • Environmentally friendly method for preparing 4,6-dihalogen-substituted indole-2-ethyl formate
  • Environmentally friendly method for preparing 4,6-dihalogen-substituted indole-2-ethyl formate

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0020] Embodiment 1, the synthesis of 3,5-dichloro-substituted indole-2-ethyl carboxylate

[0021] Ethyl pyruvate-3,5-dichlorophenylhydrazone (II) (prepared according to the document Org Pro Res Dev, 2000, 4(6):477-487) 15g is placed in a 500mL three-necked bottle, and polyphosphoric acid is preheated to 60-70°C, then weighed 35g of polyphosphoric acid and put it into a three-neck flask, added 30mL of toluene, raised the temperature to 90°C under the protection of argon, and reacted for 3 hours at a mechanical stirring speed of 120r / min. Stand still, pour out the upper layer toluene liquid, then add 30mL toluene to the reaction bottle, stir for 10min, then stand still, pour out the upper layer toluene liquid. This was repeated 3 times, the toluene solution was combined, and concentrated to dryness under reduced pressure to obtain 13.66 g of a light yellow solid with a yield of 97%. mp:187-188℃; HRMS(ESI):m / z[M-H] - Calcd. For C 11 h 8 NO 2 C l2 :255.9927; Found: 255.9930...

Embodiment 2

[0022] Embodiment 2, the synthesis of 3,5-difluoro-substituted indole-2-ethyl carboxylate

[0023] Ethyl pyruvate-3,5-difluorophenylhydrazone (II) (prepared according to the document Org Pro Res Dev, 2000, 4(6):477-487) 40g is placed in a 500mL three-necked bottle, and polyphosphoric acid is preheated to 60-70°C, then weighed 94g of polyphosphoric acid and put it into a three-neck flask, added 100mL of toluene, raised the temperature to 90°C under the protection of argon, and reacted for 3 hours at a mechanical stirring speed of 120r / min. Stand still, pour out the upper layer toluene liquid, then add 100mL toluene to the reaction bottle, stir for 10min, then stand still, pour out the upper layer toluene liquid. This was repeated 3 times, the toluene liquids were combined, and concentrated to dryness under reduced pressure to obtain 37.00 g of a light yellow solid with a yield of 99%. mp:154-155℃; HRMS(ESI):m / z[M-H] - Calcd. For C 11 h 8 NO 2 f 2 :224.0518; Found: 224.051...

Embodiment 3

[0024] Embodiment 3, the extraction rate of toluene to 3,5-difluoro-substituted indole-2-ethyl carboxylate

[0025] Ethyl pyruvate-3,5-difluorophenylhydrazone (II) (prepared according to the document Org Pro Res Dev, 2000, 4(6):477-487) 40g is placed in a 500mL three-necked bottle, and polyphosphoric acid is preheated to 60-70°C, then weighed 94g of polyphosphoric acid and put it into a three-neck flask, added 100mL of toluene, raised the temperature to 90°C under the protection of argon, and reacted for 3 hours at a mechanical stirring speed of 120r / min. Stand still, pour out the upper layer toluene liquid, then add 100mL toluene to the reaction bottle, stir for 10min, then stand still, pour out the upper layer toluene liquid. This was repeated four times, and the amount of ethyl 3,5-difluorosubstituted indole-2-carboxylate extracted by each toluene solution is shown in Table 1.

[0026] Melting point and nuclear magnetic data are consistent with embodiment 2.

[0027] Tabl...

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Abstract

The invention discloses a preparation method of 4,6-dihalogen-substituted indole-2-ethyl formate, the preparation method is characterized in that ethyl pyruvate-3,5-dihalophenylhydrazone is used as araw material for cyclizing in a polyphosphoric acid and toluene mixed solvent system to form 3,5-dihalogen-substituted indole-2-ethyl formate, and the target compound is isolated by liquid-liquid extraction of a reaction mixture. The method is simple in operation, free of waste water discharge, green, environmentally friendly and suitable for industrial production.

Description

technical field [0001] A synthesis method and post-treatment technology for preparing ethyl 4,6-dihalogen substituted indole-2-carboxylate. Background technique [0002] The Fischer indole synthesis method is recognized as the most convenient and economical method for the synthesis of indole rings. The classic Fischer indole synthesis reaction uses aliphatic aldehydes, ketones and phenylhydrazine derivatives as raw materials to condense into corresponding phenylhydrazone derivatives, and then rearrange and ring-close them under acid catalysis to finally generate indole derivatives . In recent years, on the basis of the classic liquid-phase method, researchers have carried out research on liquid-liquid two-phase method and solid-phase method, and have made some progress. However, the solid-phase method is limited by its scale, and it is difficult to meet the needs of large-scale preparations. Therefore, the liquid-phase method is more suitable for industrial production, but...

Claims

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Application Information

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IPC IPC(8): C07D209/42
CPCC07D209/42
Inventor 张翔杨旭尹大力崔华清肖琼汪小涧文辉席眉扬
Owner INST OF MATERIA MEDICA AN INST OF THE CHINESE ACAD OF MEDICAL SCI