Novel synthesis method of florfenicol

A technology of florfenicol and synthetic method, which is applied in the field of florfenicol synthesis, can solve the problems of low total yield, long route, high waste water treatment cost, etc., and achieve the goal of saving treatment cost, simple reaction steps, and reduced cost Effect

Active Publication Date: 2017-01-25
WEIFANG DAYOU BIOLOGICAL CHEM CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The disadvantages of this route include: 1. A large amount of copper sulfate wastewater is produced during the preparation of copper salt, which seriously pollutes the environment and the cost of wastewater treatment is high; 2. Only half of the required configuration intermediate is obtained by splitting and separating a single isomer, although Transformation of obsolete configurations is currently possible through epimerization / hydrolysis chemistry, but with a correspondingly large increase in reaction steps and costs
This route has the disadvantages that the enzyme catalyst is not easy to obtain in the synthetic method, the route is long, and the total yield is low.

Method used

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  • Novel synthesis method of florfenicol
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  • Novel synthesis method of florfenicol

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0030] Example 1 Preparation of (1R, 2S)-3-fluoro-1-(4-(methylsulfonyl)benzene)-2-nitropropan-1-ol (IV)

[0031] Step 1 Preparation of catalyst solution: 3Å molecular sieve, tetrahydro-salen ligand (Ia) (82 mg, 0.2 mmol), (CuOTf) 2 .C 6 H 5 CH 3 (10 mg, 0.02 mmol) was added to dichloromethane (8 mL) to prepare a catalytic solution; the added amount of the tetrahydro-salen ligand (Ia) was 10 mol of the added amount of methylsulfonyl benzaldehyde (II) %; the CuOTf) 2 .C 6 H 5 CH 3 The added amount accounts for 1 mol% of the added amount of methylsulfonyl benzaldehyde (II).

[0032] Step 2 Asymmetric Henry reaction: Add fluoronitroethane (III) (2.1 g, 0.022 mol) to the prepared catalyst solution, stir at room temperature for 10 minutes, add p-methylsulfonyl benzaldehyde (II) (3.7 g, 0.02 mol), heated to 30°C and stirred for 24 hours to perform catalytic reaction.

[0033] Step 3 Collection: Distill the materials after the catalytic reaction under reduced pressure and column chromatogr...

Embodiment 2

[0035] Example 2 Preparation of (1R,2S)-3-fluoro-1-(4-(methylsulfonyl)benzene)-2-nitropropane-1-ol (IV)

[0036] Step 1 Preparation of catalyst solution: 3Å molecular sieve, tetrahydro-salen ligand (Ib) (93 mg, 0.2 mmol), (CuOTf) 2 .C 6 H 5 CH 3 (10 mg, 0.02 mmol) was added to tetrahydrofuran (8 mL) in sequence to prepare a catalyst solution; the added amount of tetrahydro-salen ligand (Ia) was 10 mol% of the added amount of methylsulfonyl benzaldehyde (II) ; The CuOTf) 2 .C 6 H 5 CH 3 The added amount accounts for 1 mol% of the added amount of methylsulfonyl benzaldehyde (II)

[0037] Step 2 Asymmetric Henry reaction: Add fluoronitroethane III (2.1 g, 0.022 mol) to the catalyst solution, stir at room temperature for 10 minutes, add p-methylsulfonyl benzaldehyde II (3.7 g, 0.02 mol), and heat The reaction was stirred at 25°C for 24 hours, and the reaction was complete.

[0038] Step 3 Collection: The mixture after the catalytic reaction is subjected to vacuum distillation, and colu...

Embodiment 3

[0040] Example 3 Preparation of (1R, 2S)-3-fluoro-1-(4-(methylsulfonyl)benzene)-2-nitropropan-1-ol (IV)

[0041] Step 1 Preparation of catalyst solution: 3Å molecular sieve, tetrahydro-salen ligand (Ic) (104 mg, 0.2 mmol), (CuOTf) 2 .C 6 H 5 CH 3 (10 mg, 0.02 mmol) was added to toluene (8 mL) in sequence to prepare a catalytic solution; the added amount of tetrahydro-salen ligand (Ia) was 10 mol% of the added amount of methylsulfonyl benzaldehyde (II) ; The CuOTf) 2 .C 6 H 5 CH 3 The added amount accounts for 1 mol% of the added amount of methylsulfonyl benzaldehyde (II).

[0042] Step 2 Asymmetric Henry reaction: add fluoronitroethane III (2.1 g, 0.022 mol) to the catalyst solution, stir at room temperature for 10 minutes, add p-methylsulfonyl benzaldehyde II (3.7 g, 0.02 mol), and heat Stir and react at 35°C for 24 hours, and the reaction is complete.

[0043] Step 3 Collection: The materials after the catalytic reaction are subjected to vacuum distillation, and column chromatogr...

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PUM

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Abstract

The invention provides a synthesis method of florfenicol (I). The method is characterized by comprising the step of asymmetric Henry reaction: carrying out asymmetric Henry reaction on p-methylsulfuryl benzaldehyde (II) and fluoronitroethane (III) in a catalytic liquid to generate (1R,2S)-3-fluoro-1-(4-(methylsulfuryl)phenyl)-2-nitropropane-1-ol (IV). The florfenicol synthesis process does not increase the burden to the environment, and can save the pollutant treatment cost. In the florfenicol synthesis process, the reaction step is simple, thereby greatly lowering the cost. In the florfenicol synthesis process, the used catalyst is accessible, and the yield is higher.

Description

Technical field [0001] The present invention relates to the fields of organic chemistry and medicinal chemistry. Specifically, the present invention relates to a new synthetic method of florfenicol. Background technique [0002] Florfenicol is a β-amino alcohol animal-specific antibiotic developed by Schering-Plough of the United States based on thiamphenicol in 1979. Compared with thiamphenicol, it has better antibacterial activity and safety. , Effectiveness and drug resistance, no aplastic anemia, teratogenic, carcinogenic and mutagenic effects. At present, it has been widely used in aquaculture and animal husbandry to prevent and treat bacterial diseases such as fish, pigs and cattle. [0003] At present, the industrial production of florfenicol is mainly through the reaction of p-methylsulfonyl benzaldehyde with glycine and copper sulfate to prepare copper salt. After esterification, the racemic p-methylsulfonyl phenylserine ethyl ester is obtained, which is then resolved by ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07C315/04C07C317/32
CPCC07C315/04C07C317/32C07C317/14
Inventor 冯树海李峰耿洪军宋晓峰李维纳李文远
Owner WEIFANG DAYOU BIOLOGICAL CHEM CO LTD
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