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Method for synthesizing 2-normal-butyl-4-chloro-5-formylimidazole

A technology of formyl imidazole and n-butyl is applied in the field of synthesis of losartan intermediate 2-n-butyl-4-chloro-5-formyl imidazole, which can solve the problems of difficult separation and purification of products, high cost of waste treatment, Harsh reaction conditions and other problems, to achieve the effect of low cost of waste treatment, easy separation and purification, and mild reaction conditions

Active Publication Date: 2015-07-15
ZHEJIANG UNIV OF TECH +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0006] The above-mentioned methods all use a large amount of highly toxic phosphorus oxychloride, and a large amount of phosphorus-containing wastewater is produced in the industrial production process, resulting in high cost for the treatment of the three wastes, and there are disadvantages such as unsafe operation, difficult separation and purification of products, and harsh reaction conditions.

Method used

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  • Method for synthesizing 2-normal-butyl-4-chloro-5-formylimidazole
  • Method for synthesizing 2-normal-butyl-4-chloro-5-formylimidazole

Examples

Experimental program
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Effect test

Embodiment 1

[0023] In a 250mL four-neck flask equipped with a thermometer, reflux condenser and mechanical stirring, add 14g (0.1mol) of imidazolone (II), 50mL of toluene, stir to dissolve, add 21.9g of N,N-methylformamide (DMF) (0.3mol), bis(trichloromethyl)carbonate 29.7g (0.1mol), stirred for 30 minutes, then heated to 100°C for 4 hours. After the reaction is complete, add 20 mL of water, stir and hydrolyze for 10 minutes, separate the water layer after standing, extract the water layer with 20 mL of toluene, combine the toluene layers and dry with anhydrous sodium sulfate, evaporate the solvent, add ethyl acetate / petroleum ether ( Volume ratio 1:1) 80mL, after recrystallization, 14.0g light yellow solid was obtained, melting point 93-94°C, yield 75%.

Embodiment 2

[0025] In a 500mL four-necked flask equipped with a thermometer, a reflux condenser and mechanical stirring, add 28g (0.2mol) of imidazolone (II), 100mL of xylene, stir to dissolve, add N, N-diethylformamide 60.6g ( 0.6mol), bis(trichloromethyl)carbonate 59.4g (0.2mol), stirred for 30 minutes, then heated to 100°C for 4 hours. After the reaction is complete, add 30 mL of water, stir and hydrolyze for 10 minutes, separate the water layer after standing still, extract the water layer with 50 mL of xylene, combine the xylene layers and dry with anhydrous sodium sulfate, evaporate the solvent under reduced pressure, and add ethyl acetate / petroleum ether (volume ratio 1:1) 120mL, after recrystallization, 26.0g of light yellow solid was obtained, the melting point was 92-94°C, and the yield was 70%.

Embodiment 3

[0027] In a 250mL four-neck flask equipped with a thermometer, reflux condenser and mechanical stirring, add imidazolone (II) 14g (0.1mol), toluene 50mL, stir to dissolve, add N-phenyl-N-methylformamide 40.5g (0.3mol), bis(trichloromethyl)carbonate 29.7g (0.1mol), stirred for 30 minutes, then heated to 100°C for 4 hours. After the reaction is complete, add 20 mL of water, stir and hydrolyze for 10 minutes, separate the water layer after standing, extract the water layer with 20 mL of toluene, combine the toluene layers and dry with anhydrous sodium sulfate, evaporate the solvent, add ethyl acetate / petroleum ether ( Volume ratio 1:1) 80mL, 11.2g of light yellow solid was obtained after recrystallization, melting point 90-93°C, yield 60%.

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Abstract

The invention discloses a method for synthesizing 2-normal-butyl-4- chloro-5-formylimidazole shown by a formula (I). Imidazolone shown in the formula (II) reacts with bis (trichloromethyl) carbonate shown by a formula (III) and formamide shown by a formula (IV) in an organic solvent for 1-10 hours at the temperature of 20 DEG C below zero to 200 DEG C, and reaction solution is hydrolyzed to obtain 2-normal-butyl-4-chloro-5-formylimidazole. The invention has mild reaction conditions, good selectivity, no generation of phosphorus wastewater and low cost of proposal of waste water, waste gases and waste residues, and is suitable for industrial production.

Description

technical field [0001] The invention relates to a synthesis method of a losartan intermediate 2-n-butyl-4-chloro-5-formyl imidazole. Background technique [0002] 2-n-butyl-4-chloro-5-formyl imidazole is a key intermediate of losartan, a non-peptide angiotensin II receptor blocker. [0003] U.S. Patent No. 5,442,076 reports that 2-n-butyl-3,5-dihydroimidazol-4-ketone is treated with phosphorus oxide and N,N-dimethylformamide to obtain 2-n-butyl-4-chloro-5 - formyl imidazole. [0004] U.S. Patent No. 5,486,617 reported that 2-n-butyl-3,5-dihydroimidazol-4-ketone was treated with phosphorus oxychloride and N,N-dimethylformamide dimethyl acetal to obtain 2-n-butyl -4-Chloro-5-formyl imidazole. [0005] U.S. Patent No. 5,606,072 reported that 2-n-butyl-3,5-dihydroimidazol-4-ketone was first treated with chlorination reagents such as phosphorus trichloride or thionyl chloride to obtain 2-n-butyl-5-chloroimidazole, Then, in the presence of phosphorus oxychloride, react with N,...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D233/68
Inventor 金灿苏为科
Owner ZHEJIANG UNIV OF TECH
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