Method for preparing chloramphenicol

A technology of chloramphenicol and structural formula, applied in the field of compound preparation, can solve the problems of increased production cost, three wastes, long synthetic route of chloramphenicol, etc., and achieves the effects of cost reduction, low raw material price and high total yield

Active Publication Date: 2012-04-04
WUHAN WUYAO SCI & TECH
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  • Abstract
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Problems solved by technology

[0006] As can be seen from the above, the synthesis route of chloramphenicol is long at present, because the theoretical maximum yield of splitting is only 50%, calculated in terms of ethylbenzene, the actual yield of domestic production is about 30%, which makes the production cost and the three wastes increase. The aluminum propoxide reduction process also produces a large amount of three wastes that are difficult to handle, so finding a more economical synthesis method is always a challenge

Method used

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  • Method for preparing chloramphenicol

Examples

Experimental program
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Embodiment 1

[0034] 1 of the preparation of embodiment 1 (R)-2-nitro-1-phenylethanol

[0035] 0.9 g copper trifluoromethanesulfonate Cu(OTf) 2 (0.25mmol), 1.2 grams of ligand {2,6-bis[(S)-4-isopropyl-1-phenyl-4,5-dihydro-1H-2-imidazolyl]pyridine} (2.6mmol ) and 20 milliliters of 1,4-dioxane were added in a 100-milliliter single-necked flask, and the nitrogen flow was kept constant after replacing the air inside with nitrogen, cooled by an ice bath after magnetic stirring for 2 hours, and then added 2.7 grams of benzaldehyde (25 mmol) , 15 grams of nitromethane (250mmol) and N-methylmorpholine (0.27 milliliters, 2.5mmol), the reaction solution was stirred in ice-bath cooling for 24 hours, after thin plate chromatography detected no raw material benzaldehyde spots, then distillation under reduced pressure Remove volatile solvent, remove catalyst by silica gel filtration, filtrate is concentrated to obtain product 4.3 grams, yield 97%, HPLC measures e.e value to be 97%, nuclear magnetic spec...

Embodiment 2

[0036] 2 of the preparation method of embodiment 2 (R)-2-nitro-1-phenylethanol

[0037] In a 100 ml single-necked flask, add 0.5 g of 1-[2-(4S)-4-R-4,5-dihydro-2-oxazoline-ethyl]piperidine, 0.09 g of trifluoromethanesulfonate For copper (CuOTf), replace the air inside with nitrogen and keep the nitrogen flow constant. After 3 hours of magnetic stirring, cool in an ice bath, add 2.7 g of benzaldehyde (2 mol) and 15 g of nitromethane (6 mol) to anhydrous di A mixture was formed in methyl sulfoxide, and then the reaction solution was stirred in an ice bath for 12 hours. After thin-plate chromatography detected no raw material benzaldehyde spots, the volatile solvent was removed by distillation under reduced pressure, the catalyst was removed by silica gel filtration, and the filtrate was concentrated to obtain The product was 4.2 grams, the yield was 92%, and the e.e value determined by HPLC was 97%.

Embodiment 3

[0038] Example 3 Preparation of (1R, 2R)-2-nitro-1-phenyl-1,3-propanediol 1

[0039] Add 20 ml of 1,4-dioxane into a 100 ml single-necked flask, replace the air inside with nitrogen and keep the nitrogen flow constant, stir magnetically and add 0.75 g of paraformaldehyde (25 mmol), 4.2 g of (R)-2 -Nitro-1-phenylethanol (25mmol) and N-methylmorpholine (0.27 ml, 2.5mmol), the reaction solution was stirred in an ice bath for 24 hours, no raw material (R)-2- was detected by thin plate chromatography After the spots of nitro-1-phenylethanol, the volatile solvent was then distilled off under reduced pressure, purified by silica gel filtration, and the filtrate was concentrated to obtain 4.2 g of the product, with a yield of 85%. 1 H NMR (acetone-d 6 )δ: 3.46(ddd, J=3.2, 7.9, 12.0Hz, 1H), 3.70(s, 1H), 3.90(ddd, J=6.5, 9.2, 12.0Hz, 1H), 4.19~4.23(m, 2H) , 4.84 (ddd, J=3.2, 9.2, 9.2Hz, 1H), 5.08 (d, J=9.2Hz, 1H), 5.03~5.11(m, 1H), 7.31~7.48(m, 5H). 13 C NMR (acetone-d 6 )δ: 61.2, 7...

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Abstract

The invention relates to a method for preparing a broad spectrum antibiotic of chloramphenicol. The method comprises the following steps of: synthesizing (R)-2-nitro-1-benzylcarbinol by using benzaldehyde and nitromethane as raw materials in the presence of a chiral catalyst; reacting with formaldehyde to obtain (1R,2R)-2-nitro-1-benzyl-1,3-propanediol, and performing hydrogenation reduction to obtain (1R,2R)-2-amino-1-benzyl-1,3-propanediol; and performing nitration and dichloro acetylization on the intermediate at low temperature to obtain the chloramphenicol. By the method, the common chiral resolution and aluminum isopropoxide reduction in the industry at present can be avoided, three wastes are reduced, the raw materials and reagents are cheap and readily available, the method comprises a few synthesizing steps, the yield is high, and the method is more suitable for industrial production.

Description

technical field [0001] The invention relates to a preparation method of a compound, in particular to a preparation method of a broad-spectrum antibiotic chloramphenicol. Background technique [0002] Chlorotoxin is a broad-spectrum antibiotic, mainly used for typhoid bacillus, Shigella, meningococcus, pneumococcus infection, and can also be used for rickettsial infection. Although it has many side effects such as inhibition of bone marrow hematopoietic function, causing coarse cells and thrombocytopenia or aplastic anemia, it is still the drug of choice for the treatment of typhoid fever. [0003] Chloramphenicol is white or slightly yellow-green needle-like, long flaky crystals or crystalline powder. Bitter. The melting point is 149-153°C. Soluble in organic solvents such as methanol, ethanol and acetone, slightly soluble in water. Specific rotation [α] D 25 =+18.5~+21.5° (absolute ethanol). [0004] There are many reports about the synthetic route of chloramphenicol...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07C233/18C07C231/02
Inventor 杨尚金冯珂杨波郭亚兵郭婷婷丁友友谢国范
Owner WUHAN WUYAO SCI & TECH
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