ChemicalBook CAS DataBase List Torezolid

Torezolid synthesis

11synthesis methods

Product Name:Torezolid
CAS Number:856866-72-3
Molecular formula:C17H15FN6O3
Molecular Weight:370.34

444335-16-4 Synthesis

(5R)-3-(4-BROMO-3-FLUOROPHENYL)-5-HYDROXYMETHYLOXAZOLIDIN-2-ONE

444335-16-4
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380380-64-3 Synthesis

5-BROMO-2-(2-METHYL-2H-TETRAZOL-5-YL)-PYRIDINE

380380-64-3
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856866-72-3
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Yield:856866-72-3 83%

Reaction Conditions:

Stage #1:(R)-3-(4-bromo-3-fluorophenyl)-5-(hydroxylmethyl)oxazolidin-2-one with dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂;potassium acetate;bis(pinacol)diborane in dimethyl sulfoxide at 80; for 14 h;Inert atmosphere;
Stage #2:5-bromo-2-(2-methyl-2H-tetrazol-5-yl)pyridine with dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂;caesium carbonate in 1,4-dioxane;water at 70; for 3 h;Inert atmosphere;

Steps:

1 Example 1: Preparation of (R)-3-(4-(2-(2-methyltetrazol-5-yl)pyridin-5-yl)-3-fluorophenyl)-5-hydroxymethyloxazolidin-2-one (Formula V)
DMSO (100 ml) was added to a 250 ml reaction flask,(5R) -3- (4-bromo-3-fluorophenyl) -5-hydroxymethyloxazolidin-2-one(10 g, 34.5 mmol), pinacolate (17.52 g, 69 mmol),[1,1'-bis (diphenylphosphino) ferrocene] dichloropalladium dichloromethane complex (1.41 g, 1.73 mmol)And potassium acetate (13.5 g, 138 mmol), and the temperature was raised to 80 ° C under a nitrogen atmosphere,For 14 hours. The heating was stopped, the solution was cooled to room temperature, and extracted with water / ethyl acetate 3 times. The organic layers were combined and the organic layer was washed with saturated waterBrine, dried over anhydrous sodium sulfate and concentrated by suction filtration. The concentrated product of the above step was added to a 250 ml reaction flask,1,4-dioxane (100 ml) was added,5-bromo-2- (2-methyl-2H-tetrazol-5-yl) pyridine(8.28 g, 34.5 mmol),[1,1'-bis (diphenylphosphino) ferrocene] dichloropalladium dichloromethane complex (0.56 g, 0.69 mmol)And cesium carbonate aqueous solution (50 ml, containing 33.72 g of cesium carbonate, 103.5 mmol),Under nitrogen protection,The temperature was raised to 70 ° C,The reaction was carried out for 3 hours,Dichloromethane was added for extraction.The separated organic phase was washed with saturated brine,Anhydrous sodium sulfate dehydration,filter,Concentrated in vacuo and purified by column chromatography,10.6 g of a solid was obtained,The yield was 83.0%HPLC purity was 98.34% (area normalization method).

References:

Chia Tai Tianqing Pharmaceutical Group Co., Ltd.;Zhu, Yizhong;Zhang, Xiquan;Liu, Fei;Gu, Hongmei;Zhu, Bo;Tang, Song;Wang, Lulu CN105418678, 2016, A Location in patent:Paragraph 0070; 0071; 0072; 0073; 0074; 0075