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D, L-naproxen one-pot synthesis method

A synthesis method and technology of naproxen, applied in chemical instruments and methods, preparation of oxygenated compounds, preparation of carbon-based compounds, etc., can solve the problems of low reaction efficiency, long reaction time, large amount of waste water, etc., and improve the reaction efficiency , The effect of shortening the reaction time and reducing waste water discharge

Inactive Publication Date: 2019-09-20
CHONGQING MEDICAL & PHARMA COLLEGE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Select toluene, hexanaphthene, sherwood oil or n-hexane in these reaction systems because of low boiling point, low reaction efficiency, long reaction time and high cost.
[0010] Secondly, the existing production process also has defects such as large amount of waste water, low total yield and complicated operation.

Method used

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  • D, L-naproxen one-pot synthesis method
  • D, L-naproxen one-pot synthesis method
  • D, L-naproxen one-pot synthesis method

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0031]

[0032] Put 1.5 kg of xylene and 600 g (1.59 mol) of phenyltrimethylammonium tribromide into a 5 L three-necked flask, stir and dissolve at 35°C-45°C for half an hour. Then cool down to 15° C., add 320 g (1.5 mol) of 6-methoxy-2-propionylnaphthalene, continue the reaction at this temperature for 8 hours, add 1.5 kg of water to the system and stir to separate the liquid. The upper organic phase was directly used in the next reaction without further purification. The aqueous phase is collected for recovery of phenyltrimethylammonium tribromide.

[0033] Pour the xylene solution from the previous step into a 3-liter three-necked flask and heat to boiling. After azeotropic removal of water in the system, cool down to 60°C and add 115 grams (1.1 mol) of neopentyl glycol and 40 grams (0.23 mol) of p-toluenesulfonic acid. . After the addition, the temperature was raised to reflux, the reflux was divided into water and reacted for 4 hours, the raw materials disappeared as...

Embodiment 2

[0038] Put 1.5 kg of xylene and 596 g (1.58 mol) of phenyltrimethylammonium tribromide into a 5 L three-necked flask, stir and dissolve at 35°C-45°C for half an hour. Then cool down to 25° C., add 320 g (1.5 mol) of 6-methoxy-2-propionylnaphthalene, continue the reaction at this temperature for 7 hours, add 1.5 kg of water to the system and stir to separate the liquid. The upper organic phase was directly used in the next reaction without further purification.

[0039] Pour the xylene solution from the previous step into a 3-liter three-necked flask and heat to boiling. After azeotropic removal of water in the system, cool down to 80°C and add 125 grams (1.2 mol) of neopentyl glycol and 78 grams (0.45 mol) of p-toluenesulfonic acid. . After the addition, heat up to reflux, reflux and divide water for 3 hours, HPLC detects that the raw material disappears, cool down to 80°C, set aside, and proceed to the next step.

[0040] Add 0.15 mol of zinc acetate to the xylene solution ...

Embodiment 3

[0044]Put 1.5 kg of xylene and 679 g (1.8 mol) of phenyltrimethylammonium tribromide into a 5 L three-necked flask, stir and dissolve at 35°C-45°C for half an hour. Then cool down to 18° C., add 320 g (1.5 mol) of 6-methoxy-2-propionylnaphthalene, continue the reaction at this temperature for 7 hours, add 1.5 kg of water to the system and stir to separate the liquid. The upper organic phase was directly used in the next reaction without further purification.

[0045] Pour the xylene solution from the previous step into a 3-liter three-necked flask and heat to boiling. After azeotropic removal of water in the system, cool down to 70°C and add 94 grams (0.9 mol) of neopentyl glycol and 26 grams (0.15 mol) of p-toluenesulfonic acid. . After the addition, heat up to reflux, reflux and divide water for 4 hours, HPLC detects that the raw material disappears, cool down to 70°C, set aside, and proceed to the next step.

[0046] Add 24 grams (0.3 mol) of zinc oxide to the xylene solu...

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Abstract

The invention provides a D, L-naproxen one-pot synthesis method which is characterized by including the preparation steps: (1) adding xylene into a reaction vessel, performing reaction with phenyl trimethyl ammonium tribromide and 6-methoxyl-2-propionyl naphthalene to obtain xylene solution; (2) heating the xylene solution to boil and remove water, cooling the xylene solution, adding neopentyl glycol and p-toluenesulfonic acid and then continuing reflux water distribution reaction; (3) adding zinc acetate or zinc oxide into last-step reaction liquid and performing heating reflux reaction; (4) adding sodium hydroxide or potassium hydroxide solution into residues obtained by drying by distillation and dissolution in the last step, performing hydrolysis and collecting water solution for stand-by application of next-step reaction; (5) adding Raney nickel into the water solution and performing hydrogenation reaction to obtain a product. Total yield reaches 73%, one-pot synthesis is performed in whole operation, a technology is simplified, and an industrial route is environmentally friendly.

Description

technical field [0001] The invention relates to a one-pot method for synthesizing D, L-body naproxen, belonging to the field of organic synthesis. Background technique [0002] Naproxen (naproxen), whose chemical name is S-(+)-2-(6-methoxy-naphthyl) propionic acid, is a non-steroidal anti-inflammatory analgesic drug (NSAID) developed by Syntex Corporation. ), this product has strong anti-inflammatory, antipyretic and analgesic effects. Its anti-inflammatory effect is more than ten times that of phenylbutazone, its antipyretic effect is 22 times that of aspirin, and its analgesic effect is 7 times that of aspirin. Naproxen has the obvious effect of inhibiting prostaglandin synthase to reduce the release of prostaglandin, thereby playing antipyretic, analgesic and anti-inflammatory effects. It is mainly used for the treatment of rheumatoid arthritis, rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, various types of rheumatic tendonitis, periarthritis of the shou...

Claims

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Application Information

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IPC IPC(8): C07C27/02C07C51/09C07C51/377C07C59/64C07C45/63C07C49/84C07D319/06
CPCC07C45/63C07C51/09C07C51/377C07D319/06C07C59/64C07C49/84
Inventor 刘殿卿何东贤王琨郭胜超王光明吕君江
Owner CHONGQING MEDICAL & PHARMA COLLEGE
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