Structure of 403646-47-9
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CAS No. : | 403646-47-9 |
Formula : | C8H4BrF3O3 |
M.W : | 285.02 |
SMILES Code : | O=C(O)C1=CC(Br)=CC=C1OC(F)(F)F |
MDL No. : | MFCD06203214 |
Boiling Point : | No data available |
InChI Key : | KKBZEPNOWXEZSC-UHFFFAOYSA-N |
Pubchem ID : | 10946017 |
GHS Pictogram: | ![]() |
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 |
---|---|---|
49% | With lithium diisopropyl amide; In tetrahydrofuran; at -78℃; for 2h; | Under argon a solution of LDA (12.45 ml, 2M in THF) was cooled to -78C and a solution of 1-Bromo-4-trifluoromethoxy-benzene (3.7 ml) in THF (50 ml) was added slowly. The reaction mixture was stirred at -78C for two hours and dry ice was added in excess. The solvent was distilled off and the crude product was dissolved in aqueous NaOH (1N), extracted with dichloromethane, then acidified with HCl and again extracted with dichloromethane. The organic layers were dried over sodium sulphate and the solvent was removed in vacuum. The title compound was obtained in 49% yield. 1H-NMR (DMSO-d6): 13.78 s (1H); 8.05 d (J = 2.6 Hz, 1H); 7.92 dd (J = 2.6 Hz / 8.9 Hz, 1H); 7.47 dd (J = 1.3 Hz / 8.9, 1H). |
49% | 2b) 5-Bromo-2-trifluoromethoxy-benzoic acid Under argon a solution of LDA (12.45 ml, 2M in THF) was cooled to -78C and a solution of 1-Bromo-4-trifluoromethoxy-benzene (3.7 ml) in THF (50 ml) was added slowly. The reaction mixture was stirred at -78C for two hours and dry ice was added in excess. The solvent was distilled off and the crude product was dissolved in aqueous NaOH (1 N), extracted with dichloromethane, then acidified with HCl and again extracted with dichloromethane. The organic layers were dried over sodium sulphate and the solvent was removed in vacuum. The title compound was obtained in 49% yield. 1H-NMR (DMSO-d6): 13.78 s (1 H); 8.05 d (J = 2.6 Hz, 1 H); 7.92 dd (J = 2.6 Hz / 8.9 Hz, 1 H); 7.47 dd (J = 1.3 Hz / 8.9, 1 H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
37% | LDA was prepared by the dropwise addition of n-BuLi (2.5 M in hexanes, 9.96 mL, 1.2 equiv) to a solution of DIPEA (3.49 mL, 1.2 equiv) in THF (40 mL) at 0 C. under an atmosphere of nitrogen. The solution was allowed to stir for 30 min at 0 C. and then cooled to -100 C. and 1-bromo-4-trifluoromethoxybenzene (5.0 g, 1.0 equiv) was added dropwise. The reaction mixture was allowed to stir at -100 C. for 1.5 hr, carbon dioxide gas was bubbled through the solution for 45 min, and allowed to warm to -60 C. during this time. The reaction was then allowed to warm to room temperature and stirred for 18 hrs. The solvents were evaporated and the residue was dissolved in 1N NaOH (50 mL) and then washed with Et2O (2×). The aqueous phase was acidified to pH=1 by the addition of conc. HCl and then extracted with Et2O. The organic phase was dried over Na2SO4, filtered, and concentrated. The residue was purified by filtering through SiO2 (94:5:1 CH2Cl2:MeOH:AcOH) to give the carboxylic acid (2.2 g, 37%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
69% | With borane-THF; In tetrahydrofuran; at 0 - 70℃; for 18h; | To a solution of 5-bromo-2-trifluoromethoxy benzoic acid (2.2 g, 1.0 equiv) in THF (80 mL) at 0 C. under an atmosphere of nitrogen was added dropwise a solution of borane-THF (1.0 M in THF, 19.3 mL, 2.5 equiv). The solution was heated at 70 C. for 18 hr and then allowed to cool to room temperature and concentrated. The residue was dissolved in methanol and the solvent evaporated (2×). The crude product was purified by column chromatography (SiO2, 20% EtOAc in hexane) to give the desired benzylic alcohol (1.45 g, 69%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | sulfuric acid;Heating / reflux; | To a solution of 5-Bromo-2-trifluoromethoxy-benzoic acid (200 mg) in MeOH (2 ml) was added sulphuric acid (98%, 20µl) and the reaction was stirred under reflux overnight. The reaction was concentrated, then ethyl acetate (20 ml) was added. The organic phase was washed with brine (2x), dried over sodium sulphate and the solvent distilled off to yield 89% of the title compound. 1H-NMR (DMSO-d6): 8.08 d (J = 2.6 Hz, 1H); 7.97 dd (J = 2.6 Hz / 8.7 Hz, 1H); 7.52 m (1H); 3.88 s (3H). |
89% | With sulfuric acid; In water; | 2c) 5-Bromo-2-trifluoromethoxy-benzoic acid methyl ester To a solution of 5-Bromo-2-trifluoromethoxy-benzoic acid (200 mg) in MeOH (2 ml) was added sulphuric acid (98%, 20μl) and the reaction was stirred under reflux overnight. The reaction was concentrated, then ethyl acetate (20 ml) was added. The organic phase was washed with brine (2x), dried over sodium sulphate and the solvent distilled off to yield 89% of the title compound. 1H-NMR (DMSO-d6): 8.08 d (J = 2.6 Hz, 1 H); 7.97 dd (J = 2.6 Hz / 8.7 Hz, 1 H); 7.52 m (1 H); 3.88 s (3H). |
1250 mg | With sulfuric acid; at 70℃; for 16h; | To a mixture of <strong>[403646-47-9]5-bromo-2-(trifluoromethoxy)benzoic acid</strong> (1.22 g, 4.28 mmol) in methanol (5 mL) was added ]_804 (0.68 mL, 12.84 mmol). The mixture was stirred at 70 C for 16 hours. After cooling to r.t., the mixture was concentrated, the residue was diluted with H2O (50 mL) and extracted with EtOAc (100 mL x 2). The combined organic phase was washed with brine (50 mL), dried over Na2S04, filtered and concentrated to give the crude product. The crude product was purified by flash chromatography on silica gel (EtOAc in PE = 0 to 20%) to give the product (1250 mg, 4.18 mmol) as an oil. H NMR (400MHz, CDC13) _ = 8.10 (d, 1H), 7.69 (dd, 1H), 7.22 (dd, 1H), 3.95 (s, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
46% | With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In water; N,N-dimethyl-formamide; at 20℃; | 12c) N-[2-Cyano-1-(1H-indol-3-ylmethyl)-ethyl]-5-bromo-2-trifluoromethoxy-benzamide A solution of 5-Bromo-2-trifluoromethoxy-benzoic acid (2.5 g), 3-Amino-4-(1H-indol-3-yl)-butyronitrile (1.75 g), HOBt x water (1.48 g) and EDCl (1.85 g) in DMF (20 ml) was stirred overnight at ambient temperature. The reaction mixture was poured into water, extracted with ethyl acetate (3x). The combined organic layers were washed with brine and the solvent removed under vacuum. The title compound was obtained in 46 % yield after flash chromatography. 1H-NMR (DMSO-d6): 10.89 s (1 H); 8.87 d (J = 7.9 Hz, 1 H); 7.76 dd (J = 2.5 Hz / 8.7 Hz, 1 H); 7.56 d (J = 7.9 Hz, 1 H); 7.50 d (J = 2.6 Hz, 1 H); 7.39 dd (J = 1.5 Hz / 8.9 Hz, 1 H); 7.32 d (J = 8.1 Hz, 1H); 7.18 d (J = 2.3 Hz, 1 H); 7.05 m (1 H); 6.97 m (1 H); 4.35 m (1 H); 2.97 m (2H); 2.78 m (1 H); 2.68 m (1 H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
To a round bottom flask was added A (0.484) and 1,1-carbonyldiimidazole (CDT) (0.964 mmole) in DMF (3 mL). The mixture was stirred at room temperature for 30 min followed by the addition of the hydroxyacetimidamide. The resulting mixture was stirred at room temperature for another 18 hours. The reaction mixture was concentrated down and purified by preparative TLC to give B. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
To a round bottom flask was added ethyl-5-bromo-2-(trifluoromethoxy)benzoate (1.59 mmole) and sodium hydroxide (3.99 mmole) in ethanol (12 mL). The reaction mixture was refluxed for 18 hours. The mixture was concentrated down and diluted with water and washed with dichloromethane. The aqueous layer was treated with 1 N HCl to pH 4. The precipitate was filtered and air dried overnight to give A. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
42% | To a solution of <strong>[403646-47-9]5-bromo-2-(trifluoromethoxy)benzoic acid</strong> (1.0 g, 3.5 mmol) in THF (20 mL) was added sequentially at -15 C triethylamine (0.54 mL, 3.9 mmol) and ethyl chloroformate (0.37 mL, 3.9 mmol). The resulting white suspension was stirred at -5 C for 3 hrs before anhydrous MeCN (20 mL) and trimethylsilyl diazomethane (5.5 mL, 10 mmol, 2 M solution in ether) were added, The now yellow solution was allowed to warm slowly to RT over 16 hrs. The reaction was carefully quenched with theaddition of glacial acetic acid, followed by 10% aq. NaHC03. The aqueous layer was separated and back- extracted with ether. The combined organic extracts were then dried over Na2S04, filtered and the filtrate concentrated in vacuo. Further purification by way of column chromatography (S1O2, gradient elution, Hex to 2:1 (v/v) Hex: EtOAc) afforded l-(5-bromo-2-(trifluoromethoxy)phenyl)-2-diazoethanone as a yellow oil (460 mg, 42% yield). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With thionyl chloride; at 75℃; for 1h; | A suspension of <strong>[403646-47-9]5-bromo-2-(trifluoromethoxy)benzoic acid</strong> (1.14 g) in thionyl chloride (5 mL) was stirred at 75 C. for 1 h. The volatiles were removed under reduced pressure and the residue dissolved in DCM (10 mL). A solution of N,O-dimethylhydroxylamine hydrochloride (468 mg) and triethylamine (1.11 mL) in DCM (10 mL) was added and the mixture was stirred at rt for 3 h. The mixture was washed with saturated ammonium chloride solution and water, dried and the volatiles were removed under reduced pressure to yield the desired compound (87% yield). | |
With oxalyl dichloride; N,N-dimethyl-formamide; In dichloromethane; at 20℃; | 20.0 g (70.2 mmol, 1.0 equiv.) of <strong>[403646-47-9]5-bromo-2-(trifluoromethoxy)benzoic acid</strong> were stirred in 300 mL of dichloromethane at room temperature. 0.27 mL (3.51 mmol, 0.1 equiv.) of DMF and 12.2 mL (140 mmol, 2.0 equiv.) of oxalyl chloride were added and the mixture was stirred for additional 2 h at 50C after the gas formation had stopped. After concentration, 19.9 g of raw material were obtained, which were used without further purification. | |
With oxalyl dichloride; In dichloromethane; N,N-dimethyl-formamide; at 0 - 20℃; for 2h; | To <strong>[403646-47-9]5-bromo-2-(trifluoromethoxy)benzoic acid</strong> 10a (10.0 g, 35.1 mmol) at 0 CAdd oxalyl chloride (12 mL, 138 mmol) to a solution of dichloromethane (100 mL)And N,N-dimethylformamide (0.1 mL, 1.29 mmol), and the mixture was stirred and stirred at room temperature for 2 hr.After the reaction is completed, the organic solvent is removed by concentration under reduced pressure.The title compound 10b (10.7 g, yellow oil) was obtained.Yield: 100%. Used directly in the next step. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | Intermediate 30a) A suspension of <strong>[403646-47-9]5-bromo-2-(trifluoromethoxy)benzoic acid</strong> (1.14 g) in thionyl chloride (5 mL) was stirred at 75 C for 1 h. The volatiles were removed under reduced pressure and the residue dissolved in DCM (10 mL). A solution of Λ/,Ο-dimethylhydroxylamine hydrochloride (468 mg) and triethylamine (1.11 mL) in DCM (10 mL) was added and the mixture was stirred at rt for 3 h. The mixture was washed with saturated ammonium chloride solution and water, dried and the volatiles were removed under reduced pressure to yield the desired compound (87% yield). | |
To a stirred solution of <strong>[403646-47-9]5-bromo-2-(trifluoromethoxy)benzoic acid</strong> (CAS 403646-47-9, from Combi- blocks, 10.0 g, 35.08 mmol) in THF (100 mL) was added DIPEA (13.57 g, 17.9 mL, 105.25 mmol) and HATU (20.0 g, 52.62 mmol) in portions at 0 C. After 30 min, N,O-dimethylhydroxyl amine HC1 (4.45 g, 45.61 mmol) was added at 0 C. The mixture was slowly warmed to rt and stirred for 3 h, then poured into ice-cold water (300 mL) and extracted with EtOAc (3 x 150 mL). The combined organic phases were dried over Na2SO4and concentrated under reduced pressure to yield 5-bromo-N-methoxy- N-methyl-2-(trifluoromethoxy)benzamide (12.2 g, quantitative yield). This crude material was used directly in the next step.FCMS: Method C, 1.69 min; MS: ES+: 327.8, 329.8. | ||
To a stirred solution of <strong>[403646-47-9]5-bromo-2-(trifluoromethoxy)benzoic acid</strong> (CAS 403646-47-9, from Combi- blocks, 10.0 g, 35.08 mmol) in THF (100 mL) was added DIPEA (13.57 g, 17.9 mL, 105.25 mmol) and HATU (20.0 g, 52.62 mmol) in portions at 0 C. After 30 min, N,O-dimethylhydroxyl amine HC1 (4.45 g, 45.61 mmol) was added at 0 C. The mixture was slowly warmed to rt and stirred for 3 h, then poured into ice-cold water (300 mL) and extracted with EtOAc (3 x 150 mL). The combined organic phases were dried over Na2SO4and concentrated under reduced pressure to yield 5-bromo-N-methoxy- N-methyl-2-(trifluoromethoxy)benzamide (12.2 g, quantitative yield). This crude material was used directly in the next step.FCMS: Method C, 1.69 min; MS: ES+: 327.8, 329.8. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | 5-bromo-2- (trifluoromethoxy) benzoic acid (3.00 g, 10.53 mmol) in methanol (30 ml) solution of was added dropwise concentrated sulfuric acid (300 μl). Under an argon atmosphere, and stirred under reflux conditions overnight. After completion of the reaction, concentrated to dryness. Saturated saline, a saturated aqueous solution of sodium hydrogen carbonate was added, and the mixture was extracted with chloroform. Dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure.In ethanol (30 ml) solution of the residue, was added dropwise hydrazine monohydrate (4.1 ml, 84 mmol). Under an argon atmosphere, it was stirred for 5 hours at reflux conditions,It was solidified after the completion of the reaction concentrated to dryness.In triethyl orthoformate of the residue (10.5 ml, 63 mmol) solution, paraTosylate monohydrate (200 mg, 1.1 mmol) was added dropwise. Under an argon atmosphere, was stirred for 6 hours at reflux conditions, it was solidified after completion of the reaction concentrated to dryness. The residue was purified by silica gel column chromatography (hexane / ethyl acetate) to give the title compound (2.096 g, 65%). |
Tags: 403646-47-9 synthesis path| 403646-47-9 SDS| 403646-47-9 COA| 403646-47-9 purity| 403646-47-9 application| 403646-47-9 NMR| 403646-47-9 COA| 403646-47-9 structure
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Code | Phrase |
P501 | Dispose of contents/container to ... |
P502 | Refer to manufacturer/supplier for information on recovery/recycling |
Physical hazards | |
Code | Phrase |
H200 | Unstable explosive |
H201 | Explosive; mass explosion hazard |
H202 | Explosive; severe projection hazard |
H203 | Explosive; fire, blast or projection hazard |
H204 | Fire or projection hazard |
H205 | May mass explode in fire |
H220 | Extremely flammable gas |
H221 | Flammable gas |
H222 | Extremely flammable aerosol |
H223 | Flammable aerosol |
H224 | Extremely flammable liquid and vapour |
H225 | Highly flammable liquid and vapour |
H226 | Flammable liquid and vapour |
H227 | Combustible liquid |
H228 | Flammable solid |
H229 | Pressurized container: may burst if heated |
H230 | May react explosively even in the absence of air |
H231 | May react explosively even in the absence of air at elevated pressure and/or temperature |
H240 | Heating may cause an explosion |
H241 | Heating may cause a fire or explosion |
H242 | Heating may cause a fire |
H250 | Catches fire spontaneously if exposed to air |
H251 | Self-heating; may catch fire |
H252 | Self-heating in large quantities; may catch fire |
H260 | In contact with water releases flammable gases which may ignite spontaneously |
H261 | In contact with water releases flammable gas |
H270 | May cause or intensify fire; oxidizer |
H271 | May cause fire or explosion; strong oxidizer |
H272 | May intensify fire; oxidizer |
H280 | Contains gas under pressure; may explode if heated |
H281 | Contains refrigerated gas; may cause cryogenic burns or injury |
H290 | May be corrosive to metals |
Health hazards | |
Code | Phrase |
H300 | Fatal if swallowed |
H301 | Toxic if swallowed |
H302 | Harmful if swallowed |
H303 | May be harmful if swallowed |
H304 | May be fatal if swallowed and enters airways |
H305 | May be harmful if swallowed and enters airways |
H310 | Fatal in contact with skin |
H311 | Toxic in contact with skin |
H312 | Harmful in contact with skin |
H313 | May be harmful in contact with skin |
H314 | Causes severe skin burns and eye damage |
H315 | Causes skin irritation |
H316 | Causes mild skin irritation |
H317 | May cause an allergic skin reaction |
H318 | Causes serious eye damage |
H319 | Causes serious eye irritation |
H320 | Causes eye irritation |
H330 | Fatal if inhaled |
H331 | Toxic if inhaled |
H332 | Harmful if inhaled |
H333 | May be harmful if inhaled |
H334 | May cause allergy or asthma symptoms or breathing difficulties if inhaled |
H335 | May cause respiratory irritation |
H336 | May cause drowsiness or dizziness |
H340 | May cause genetic defects |
H341 | Suspected of causing genetic defects |
H350 | May cause cancer |
H351 | Suspected of causing cancer |
H360 | May damage fertility or the unborn child |
H361 | Suspected of damaging fertility or the unborn child |
H361d | Suspected of damaging the unborn child |
H362 | May cause harm to breast-fed children |
H370 | Causes damage to organs |
H371 | May cause damage to organs |
H372 | Causes damage to organs through prolonged or repeated exposure |
H373 | May cause damage to organs through prolonged or repeated exposure |
Environmental hazards | |
Code | Phrase |
H400 | Very toxic to aquatic life |
H401 | Toxic to aquatic life |
H402 | Harmful to aquatic life |
H410 | Very toxic to aquatic life with long-lasting effects |
H411 | Toxic to aquatic life with long-lasting effects |
H412 | Harmful to aquatic life with long-lasting effects |
H413 | May cause long-lasting harmful effects to aquatic life |
H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
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