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Preparation methods of N-phenylacetyl-L-proline, and N-(1-(phenylacetyl)-L-prolyl)glycine ethyl ester

A technology of glycine ethyl ester and proline, applied in organic chemistry, peptides, etc., can solve the problems of unfavorable industrial production, low synthesis content, and low synthesis efficiency, and achieve high preparation efficiency, simple operation, and high preparation effect

Inactive Publication Date: 2015-07-22
SHANGHAI XUXIN CHEM
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0002] N-[1-(phenylacetyl)-L-prolyl]glycine ethyl ester, trade name NOOPEPT, is used to treat diseases such as obesity, alcohol-dependent degeneration or toxic injury. At present, there is no medicine for this compound in China. Reports on the synthesis process, the synthesis process that has appeared abroad, the synthesis efficiency is low, the synthesis content is low, and the purity is poor, which is not conducive to industrial production

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  • Preparation methods of N-phenylacetyl-L-proline, and N-(1-(phenylacetyl)-L-prolyl)glycine ethyl ester

Examples

Experimental program
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Effect test

Embodiment 1

[0031] The preparation method of embodiment 1N-phenylacetyl-L-proline

[0032] Put 57.5kg of L-proline into the reaction kettle, then put in 250L of 2mol / l NaOH solution, stir for 30 minutes, the temperature is controlled at -10 to -5°C, and then double dropwise add 66L of phenylacetyl chloride and 125L of 4mol / l NaOH Liquid, the temperature is controlled at -10 to -5°C, after the dropwise addition, keep warm for 15 minutes, after the end, extract with 300L ethyl acetate, separate layers, remove the ethyl acetate layer, adjust the pH to 3 with 2mol / L hydrochloric acid, and then use 300L dichloromethane extraction, partition water layer, dichloromethane layer with 20kg anhydrous NaSO Dry, filter, filtrate decompression distillation, obtain oily matter 62kg, after cooling, N-phenylacetyl-L-proline is obtained, and its purity is 99.6%.

Embodiment 2

[0033] The preparation method of embodiment 2N-phenylacetyl-L-proline

[0034] Put 50kg of L-proline into the reaction kettle, then put into 250L 2mol / l potassium hydroxide solution, stir for 30 minutes, the temperature is controlled at -10 to -5°C, then double dropwise add 56L of phenylacetyl chloride and 125L of 4mol / l Potassium hydroxide solution, the temperature is controlled at -10 to -5°C, after the dropwise addition, keep warm for 15 minutes, after the end, extract with 300L ethyl acetate, separate layers, remove the ethyl acetate layer, and adjust the pH to 1.2 with 2mol / L hydrochloric acid , then extracted with 300L dichloromethane, partitioned the water layer, and the dichloromethane layer was dried with 20kg of anhydrous NaSO4, filtered, and the filtrate was distilled under reduced pressure to obtain 62kg of oily matter, and after cooling, N-phenylacetyl-L-proline was obtained. The purity is 99.7%.

Embodiment 3

[0035] The preparation method of embodiment 3N-phenylacetyl-L-proline

[0036] Put 57.5kg of L-proline into the reaction kettle, then put into 250L 2mol / l potassium hydroxide solution, stir for 30 minutes, control the temperature at -10 to -5°C, then add dropwise 60L of phenylacetyl chloride and 125L of 4mol / l Potassium hydroxide solution, the temperature is controlled at -10 to -5°C, after the dropwise addition, keep warm for 15 minutes, after the end, extract with 300L ethyl acetate, separate layers, remove the ethyl acetate layer, and adjust the pH to 1.2 with 2mol / L hydrochloric acid , and then extracted with 300L dichloromethane, the water layer was partitioned, the dichloromethane layer was dried with 20kg anhydrous calcium chloride, filtered, the filtrate was distilled under reduced pressure to obtain 62kg of oily matter, and N-phenylacetyl-L-proline was obtained after cooling acid, its purity is 99.5%.

[0037] The N-phenylacetyl-L-proline prepared above is detected b...

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Abstract

The invention provides a preparation method of N-phenylacetyl-L-proline. The preparation method comprises following steps: 1) L-proline is mixed with a strong base solution a, and phenylacetyl chloride and a strong base solution b are added via double dropwise adding for reaction; 2) after reaction of the step 1), ethyl acetate is used for extraction, and an ethyl acetate layer is removed so as to obtain a product aqueous layer; 3) pH value of the product aqueous layer obtained via step 2) is adjusted to be lower than 7, dichloromethane is used for extraction, and a water layer is removed; and 4) a neutral drying agent is added, an obtained mixture is filtered, and an obtained filtrate is subjected to distillation and cooling so as to obtain N-phenylacetyl-L-proline. The invention also discloses a preparation method of N-(1-(phenylacetyl)-L-prolyl)glycine ethyl ester. Operation of the preparation methods is simple; and preparation efficiency is high.

Description

technical field [0001] The invention relates to the field of chemical synthesis, in particular to a preparation method of N-phenylacetyl-L-proline and N-[1-(phenylacetyl)-L-prolyl]glycine ethyl ester. Background technique [0002] N-[1-(phenylacetyl)-L-prolyl]glycine ethyl ester, trade name NOOPEPT, is used to treat diseases such as obesity, alcohol-dependent degeneration or toxic injury. At present, there is no medicine for this compound in China. According to reports on synthetic techniques, the synthetic techniques that have emerged abroad have low synthesis efficiency, low synthetic content, and poor purity, which is not conducive to industrial production. Contents of the invention [0003] The present invention proposes a method for efficiently producing N-[1-(phenylacetyl)-L-prolyl]glycine ethyl ester. [0004] The technical scheme adopted in the present invention is as follows: [0005] N-[1-(phenylacetyl)-L-prolyl] in the research of the synthetic technology of g...

Claims

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Application Information

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IPC IPC(8): C07D207/16C07K5/078
CPCC07D207/16C07K5/06165
Inventor 严建祥张卫军
Owner SHANGHAI XUXIN CHEM
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