Synthetic method for (4R,5R)-2-bischloromethyl-4,5-dihydro-5-(4-methylsulfonyl)-4-oxazole methyl alcohol

A technology of methylsulfonyl phenyl and dichloromethyl is applied in the field of synthesizing florfenicol intermediates, and can solve the problems of difficult treatment of copper-containing wastewater, low total yield and high cost, and achieve high total yield, Improve efficiency and protect the environment

Active Publication Date: 2016-01-06
SHANDONG GUOBANG PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] The disadvantages of this synthetic method are: one is that a large amount of copper-containing wastewater is difficult to handle when preparing copper salt; the other is that the synthetic route is a "linear"

Method used

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  • Synthetic method for (4R,5R)-2-bischloromethyl-4,5-dihydro-5-(4-methylsulfonyl)-4-oxazole methyl alcohol
  • Synthetic method for (4R,5R)-2-bischloromethyl-4,5-dihydro-5-(4-methylsulfonyl)-4-oxazole methyl alcohol
  • Synthetic method for (4R,5R)-2-bischloromethyl-4,5-dihydro-5-(4-methylsulfonyl)-4-oxazole methyl alcohol

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0034] (1) Take 91.1 g of 2-nitroethanol and add it to a four-necked flask with mechanical stirring, cool and control the temperature -10 to 0° C., slowly add 192.0 g of sodium hydroxide aqueous solution with a mass concentration of 25% under stirring, drop Continue to react for 20 minutes after the addition is complete, then add 191.8g of bromine dropwise, continue to complete the reaction after the dropwise addition, vacuum distillation and rectification separation to obtain 156.4g of 2-bromo-2-nitroethanol, the yield is 92.0%, the content 99.2%;

[0035] (2) Take 85.0 g of 2-bromo-2-nitroethanol in an autoclave, add 250.0 g of ethanol, drop in 5.0 g of palladium carbon, feed hydrogen to 0-0.1 MPa and supplement hydrogen during the reaction to keep the Pressure, react at 20-30°C until the pressure remains constant, filter the reaction solution to recover the catalyst, and rectify the filtrate to obtain 66.6g of 2-bromo-2-aminoethanol, with a yield of 95.1% and a content of 9...

Embodiment 2

[0040] (1) Get 91.1 g of 2-nitroethanol and add it to a four-necked flask with mechanical stirring, cool and control the temperature -10 to 0° C., slowly add 168.0 g of aqueous sodium hydroxide solution with a mass concentration of 25% under stirring, dropwise Continue to react for 20 minutes after the addition is complete, then add 167.8g of bromine dropwise, continue to complete the reaction after the dropwise addition, vacuum distillation and rectification separation to obtain 168.3g of 2-bromo-2-nitroethanol, the yield is 99.0%, the content 99.5%;

[0041] (2) Take 85.0 g of 2-bromo-2-nitroethanol in an autoclave, add 250.0 g of ethanol, drop in 5.0 g of palladium carbon, feed hydrogen to 0.1-0.2 MPa and supplement hydrogen during the reaction to keep the Pressure, react at 20-30°C until the pressure remains constant, filter the reaction solution to recover the catalyst, and rectify the filtrate to obtain 69.5g of 2-bromo-2-aminoethanol, with a yield of 99.3% and a content...

Embodiment 3

[0046] (1) Get 91.1 g of 2-nitroethanol and add it to a four-necked flask with mechanical stirring, cool and control the temperature -10 to 0° C., slowly add 144.0 g of aqueous sodium hydroxide solution with a mass concentration of 25% under stirring, drop Continue to react for 20 minutes after the addition, then add 143.8g of bromine dropwise, continue to complete the reaction after the dropwise addition, vacuum distillation and rectification separation to obtain 152.1g of 2-bromo-2-nitroethanol, the yield is 89.5%, the content 99.4%;

[0047] (2) Take 85.0 g of 2-bromo-2-nitroethanol in an autoclave, add 250.0 g of ethanol, drop in 5.0 g of palladium carbon, feed hydrogen to 0.1-0.2 MPa and supplement hydrogen during the reaction to keep the Pressure, react at 0-10°C until the pressure remains constant, filter the reaction solution to recover the catalyst, and rectify the filtrate to obtain 65.7g of 2-bromo-2-aminoethanol, with a yield of 93.8% and a content of 99.5%;

[00...

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Abstract

The invention belongs to the technical field of synthesis of a florfenicol intermediate and particularly relates to a synthetic method for (4R,5R)-2-bischloromethyl-4,5-dihydro-5-(4-methylsulfonyl)-4-oxazole methyl alcohol. The method comprises the following steps that a sodium hydroxide water solution is added into 2-nitro ethyl alcohol in a dripped mode, then bromine is added, and the reaction is carried out to obtain 2-bromine-2-nitro ethyl alcohol; 2-bromine-2-nitro ethyl alcohol and ethyl alcohol are obtained, a hydrogenation catalyst is added, the mixture reacts with hydrogen, alcohols solvent is added, and then dichloroacetonitrile is added in a dripped mode for reaction; magnesium, tetrahydrofuran and 4- methylsulfonyl benzaldehyde are added to obtain a ring compound II; the ring compound II is subjected to an isomerization reaction in the alcohols solvent to obtain (4R,5R)-2-bischloromethyl-4,5-dihydro-5-(4-methylsulfonyl)-4-oxazole methyl alcohol. According to the method, a brand-new synthetic route is adopted, and generation of a large amount of copper-containing wastewater difficult to treat is avoided; hydrogen is adopted for reduction, generation of a large number of three wastes is avoided, cost is reduced, the total yield is high and is over 98%, benefits are increased, and environment is protected.

Description

technical field [0001] The invention belongs to the technical field of synthesis of florfenicol intermediates, in particular to (4R,5R)-2-dichloromethyl-4,5-dihydro-5-(4-thiamphenicolphenyl)-4- Synthetic method of oxazole methanol. Background technique [0002] The structural formula of Florfenicol intermediate (4R,5R)-2-dichloromethyl-4,5-dihydro-5-(4-thiamphenicolphenyl)-4-oxazolemethanol is: [0003] [0004] Florfenicol is a veterinary antibiotic commonly used at present. It has a broad antibacterial spectrum and strong antibacterial effect. It has the characteristics of high safety, non-toxicity, and no residue. Used in farms, mainly for the treatment of cattle respiratory diseases caused by Pasteurella and Haemophilus. It has a good curative effect on cattle foot rot caused by Fusobacterium. It is also used for infectious diseases of pigs and chickens and bacterial diseases of fish caused by sensitive bacteria. [0005] Florfenicol is not easy to produce drug re...

Claims

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Application Information

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IPC IPC(8): C07D263/14
CPCC07D263/14
Inventor 王伟宏崔振邦何泽骁闵娜乔建超廖仕学李琦斌杨俊德
Owner SHANDONG GUOBANG PHARMA
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