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CAS No. : | 320-51-4 |
Formula : | C7H5ClF3N |
M.W : | 195.57 |
SMILES Code : | C1=C(C=CC(=C1C(F)(F)F)Cl)N |
MDL No. : | MFCD00007846 |
InChI Key : | ASPDJZINBYYZRU-UHFFFAOYSA-N |
Pubchem ID : | 67574 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine; In dichloromethane; | 2-ethoxy-6-pentadecyl-benzoyl chloride was condensed with 5-amino-2-chloro benzenetriflouride in dichloromethane in presence of triethylamine as acid scavenger to yield N-(4-Chloro-3-trifluoromethyl-phenyl)-2-ethoxy-benzamide. The reaction mixture was then concentrated in vacuo and the residue was extracted into ethyl acetate. The ethyl acetate layer was washed with water and with cold aqueous hydrochloric acid, then dried over sodium sulphate and finally concentrated in vacuo. The residue obtained was chromatographed over silica gel to afford the desired product. m/z: 344.4 (M+1),239,149,121,102,82,57 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogenchloride; tetrafluoroboric acid; sodium nitrite; In water; ethyl acetate; | EXAMPLE S 1-Chloro-4-fluoro-2-(trifluoromethyl)benzene 4-Chloro-3-(trifluoromethyl)benzenamine (19.5 g, 100 mmoles), water (40 ml) and c.hydrochloric acid (40 ml) were heated with stirring on a steam bath until a white solid formed. The mixture was cooled (ice-salt bath) and a solution of sodium nitrite (7 g, 101 mmoles) in water (15 ml) was added over 15 mins. After stirring for a further hour at 0, tetrafluoroboric acid (30 g of 40% aqueous solution) was added dropwise over 15 minutes. After one hour the solid was filtered off, washed with water (10 ml), methanol (30 ml) and ether (30 ml) and then dried in vacuo. The dry compound was heated at 140-180 until no more fumes were observed. The cooled residue was dissolved in ethyl acetate, washed with 5% aqueous sodium hydroxide, dried Na2 SO4) and the solvent was removed in vacuo. The residue was distilled in vacuo (12 mmHg, oven temperature 50-55) to give the sub-title compound as a colourless oil (7.5 g). M+ 200/198; nmr (CDCl3)delta7.8-7.2 (m). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In neat (no solvent); at 160℃; | General procedure: A mixture of compound 3 (0.2 g, 1.03 mmol) and the appropriate aniline (1.03 mmol) were reacted neat at 160 C for 10-120 minutes. The reaction mixture was cooled, dissolved in DCM and concentrated under reduced pressure to afford the desired product, which was used directly in the next step without further purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96.8% | With dmap; In N,N-dimethyl-formamide; at 140℃; for 4h;Green chemistry; | To the reaction flask, a compound IV 13.27 g, a compound V 9.93 g, a methyl isobutyryl acetate 7.32 g, a 4-dimethylaminopyridine 6.21 g, and 800 ml of DMF were sequentially added, and the mixture was stirred and dissolved, and the temperature was controlled at 140 C for 4 h. The TLC monitors the completion of the reaction. The reaction was stopped, the temperature was lowered to room temperature, and ethyl acetate was added for extraction. The organic layer was separated and concentrated under reduced pressure to give 25.55 g, product yield 96.8%, purity 99.93%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96.2% | With tetra(n-butyl)ammonium hydroxide; In tetrahydrofuran; at 35℃; for 1.33333h;Green chemistry; | The above 47 mmol of intermediate I, 3-trifluoromethyl-4-chloroaniline 46 mmol and 0.425 mmol of tetrabutylammonium hydroxide were dissolved in 80 mL of tetrahydrofuran.50 mmol of dimethyl sulphate was added dropwise in portions, and the mixture was heated to 35 C for 80 min, cooled to room temperature, and the reaction mixture was concentrated under reduced pressure, and then added to 90 mL of CH2Cl2-EtOAc (7:2).Stir, layer, respectively, wash with 30mL 5% HCl, 50mL H2O, dry Na2SO4,Filtration, concentration under reduced pressure, at least, and solids were precipitated to give a crude product of 21.16 g of crude product, 95.3%. _: Example 3-1 Regohini pure product 10 g of the crude product was added to 150 mL of water, stirred well, and the pH was adjusted to 2.0 to 2.5 with a 10% diluted aqueous hydrochloric acid solution, and stirred at room temperature.The crude product is dissolved and filtered to obtain a crude solution, and the organic impurities are extracted with diethyl ether, and the organic phase is separated;To the aqueous layer, a 6% sodium hydrogencarbonate solution was added dropwise, the pH was adjusted to 6.5-7.0, and the reaction product was precipitated and suction filtered to obtain a solid;The obtained solid was dissolved in 50 mL of diethyl ether, activated carbon was added, and heated to 30 C.Stir well, filter to obtain the filtrate, after stirring, separate the organic layer, (3 * 20mL) H2O wash, dry, filtered, distilled ether to give a thick liquid product,The viscous liquid product is added to cold water, crystals are precipitated, crystallized, filtered, and drained.A white solid was obtained, which was dried in vacuo to give 9.92 g of the crude product of rugofene, yield 96.2%, purity 99.99%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
21.99 g | With cetyltrimethylammonium hydroxide; In dichloromethane; at 35℃; for 1.33333h; | The above 49 mmol intermediate I, 3 - trifluoromethyl -4 - chloroaniline 48 mmol and 0.45 mmol cetyl trimethyl ammonium hydroxide dissolved in 80 ml dichloromethane in, batch dropping ethylene carbonate 50 mmol, heating up to 35 C reaction under 80 min, cooling to room temperature, the reaction liquid concentrated under reduced pressure, adding 90 ml CH2Cl2- EtOAc (7:2) in, stirring, layered, respectively for the 30 ml 5% HCl, 50 ml H2O washing, Na2SO4Dry, filtered, concentrated under reduced pressure to a small amount of, precipitated solid,regorafenib 21.99 g, yield 94.9%. |