Preparation method of high-purity propofol

A technology of propofol and purity, applied in the field of preparation of high-purity propofol, can solve problems such as equipment corrosion, achieve the effects of simple process, simplified preparation process and reduced production cost

Active Publication Date: 2014-12-10
四川国瑞药业有限责任公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

The Chinese patent with the publication number CN101538191 discloses a synthesis method of high-purity propofol, using 2-isopropylphenol and propylene as raw materials, catalyzed by Lewis acids such as triethylaluminum, and reacting at a pressure of 0.4-0.6Mpa to synthesize High-purity propofol, but its highest purity is only 92.7%, and the purity of raw material 2-isopropylphenol is required to be more than 99%; the U.S. patent application with publication number US5589598 discloses a high-purity propofol preparation method , acylate propofol to obtain a solid ester, after purification, then hydrolyze and distill under reduced pressure to obtain propofol with a purity of more than 99%. , acid chloride is sensitive to moisture and corrosive to equipment

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Examples

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Embodiment 1

[0042] Example 1: 2,6-diisopropylphenol (178g; 1mol) was dissolved in 200ml of DMF (N,N'-dimethylformamide), keeping the temperature below 25°C, adding potassium carbonate (152g , 1.1mol), after stirring for half an hour, p-nitrobenzyl bromide (238g, 1.1mol) was added dropwise, and the temperature was controlled not to exceed 25°C. After the dropwise addition, the reaction was incubated for 4 hours. After the reaction, add 600ml of water, extract three times with 300ml of dichloromethane, wash the dichloromethane layer once with 200ml of saturated brine, dry over anhydrous sodium sulfate, and concentrate to dryness under reduced pressure to obtain 266.38g of oil, with a yield of 85%.

[0043] Dissolve the oil in 2000ml of ethanol, add ferric chloride (25.93g, 0.16mol) and activated carbon (25.20g, 2.10mol), stir and heat up to 80°C, slowly add 80% hydrazine hydrate (311ml, 5.1 mol), after dropping, keep it warm for 2 hours, filter while hot, and concentrate the filtrate to dr...

Embodiment 2

[0047]Dissolve 2,6-diisopropylphenol (178g; 1mol) in 200ml of acetone, keep the temperature below 25°C, add potassium carbonate (152g, 1.1mol) in batches, stir for half an hour, then add p-nitrobenzyl dropwise Bromine (238g, 1.1mol), control the temperature not to exceed 25°C. After the dropwise addition, the reaction was incubated for 4 hours. After the reaction, add 600ml of water, extract three times with 300ml of dichloromethane, wash the dichloromethane layer once with 200ml of saturated brine, dry over anhydrous sodium sulfate, and concentrate to dryness under reduced pressure to obtain 266.38g of oil, with a yield of 85%.

[0048] Dissolve the oil in 2000ml of ethanol, add stannous chloride dihydrate (959g, 4.23mol), and react at 70°C for 4h. After the reaction, cool to room temperature, concentrate to dryness, add 500ml of water, adjust the pH to above 11 with 10% aqueous sodium hydroxide solution, extract three times with 300ml of ethyl acetate, dry over anhydrous so...

Embodiment 3

[0052] 2,6-Diisopropylphenol (89g; 0.5mol) was dissolved in 100ml tetrahydrofuran, keeping the temperature below 25°C, adding sodium carbonate (58.3g, 0.55mol) in batches, stirring for half an hour, then adding p-nitrogen dropwise Benzyl benzyl bromide (119g, 0.55mol), control the temperature not to exceed 25°C. After the dropwise addition, the reaction was incubated for 4 hours. After the reaction, add 300ml of water, extract three times with 150ml of dichloromethane, wash the dichloromethane layer once with 100ml of saturated brine, dry over anhydrous sodium sulfate, and concentrate to dryness under reduced pressure to obtain 120g of oil, with a yield of 76.5%.

[0053] Dissolve the oil in 1000ml of ethanol, add ferric chloride (11.67g, 0.07mol) and activated carbon (11.34g, 0.95mol), stir and heat up to 80°C, slowly add 80% hydrazine hydrate (140ml, 2.30 mol), after dropping, keep it warm for 2 hours, filter while hot, and concentrate the filtrate to dryness to obtain 94.9...

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Abstract

The invention discloses a preparation method of high-purity propofol. The method comprises the steps shown below, wherein R is selected from chlorine, bromine or sulfonate. The method provided by the invention is advantaged in intelligent idea, simple process, and suitability for industrialized productions. The purity of the prepared propofol is above 99.9%, and the prepared propofol satisfies various medical pharmaceutical standards.

Description

technical field [0001] The invention belongs to the technical field of chemical pharmacy and relates to a preparation method of high-purity propofol. Background technique [0002] Propofol (chemical name: 2,6-diisopropylphenol) is a new fast and short-acting intravenous anesthetic commonly used clinically for induction of anesthesia, maintenance of anesthesia, and sedation of critically ill ICU patients. It has Anesthesia induction has quick onset, rapid recovery and complete functional recovery, and a low incidence of postoperative nausea and vomiting. [0003] In the traditional synthesis process, the preparation method of propofol is to use aluminum phenate as a catalyst, and then carry out the alkylation reaction of phenol and propylene under the conditions of high temperature and high pressure. Since the reaction needs to be carried out under the condition of high temperature and high pressure, and the exotherm is severe, it is difficult to control the reaction accurat...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07C39/06C07C37/055
Inventor 王一茜肖捷李强国
Owner 四川国瑞药业有限责任公司
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