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CAS No. : | 103962-05-6 | MDL No. : | MFCD00042411 |
Formula : | C7H4F3IO | Boiling Point : | No data available |
Linear Structure Formula : | - | InChI Key : | RTUDBROGOZBBIC-UHFFFAOYSA-N |
M.W : | 288.01 | Pubchem ID : | 2777294 |
Synonyms : |
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Signal Word: | Warning | Class: | |
Precautionary Statements: | P261-P305+P351+P338 | UN#: | |
Hazard Statements: | H315-H319-H335 | Packing Group: | |
GHS Pictogram: |
* 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 2,2,6,6-tetramethylheptane-3,5-dione; caesium carbonate;copper(l) chloride; In 1-methyl-pyrrolidin-2-one; at 100℃; for 5h; | A solution of 4-bromophenol (0.173 g) in 4 mL of 1-methyl-2-pyrrolidone under argon atmosphere was treated with 4-(trifluoromethoxy)iodobenzene (0.313 mL), 2,2,6,6-tetramethylheptane-3,5-dione (0.046 mL) and caesium carbonate (0.652 g). The slurry was degassed by bubbling argon for 15 min and copper(I) chloride (0.099 g) was added. The reaction mixture was degassed by bubbling argon for 15 min, then heated to 100 C under argon for 5 h. The reaction mixture was cooled to room temperature and added dropwise to 30 mL of tert-butyl-methyl-ether. The slurry was filtered and the solids washed with tert-butyl-methyl-ether (3x20 mL). The combined filtrates were washed subsequently with 1N NaOH (50 mL), water (50 mL), 2N HCl (50 mL), 1N HCl (50 mL), water (50 mL) and brine (50 mL). The resulting organic layer was dried over Na2SO4 and concentrated to give a crude product which was purified by column chromatography on silica gel eluting with hexane to afford 0.15 g of the title compound as a colourless liquid. 1H-NMR(d, ppm, CDCl3): 7.45(m, 2H); 7.20(m, 2H); 6.99(m, 2H); 6.90(m, 2H) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
44% | With potassium carbonate; copper(I) bromide; In N-methyl pyrrolidinone;Heating / reflux; | A mixture of 0.6 g (2.6 MMOL) 5- (4-TRIFLUOROMETHOXY-PHENYL)-1 H-INDOLE, 0.53 mL (2.8 MMOL) 4- (TRIFLUOROMETHOXY) iodobenzene, 0.075 g (0.52 MMOL) copper (L) bromide and 0.54 g (3.9 MMOL) K2CO3 in 10 mL anhydrous N-methyl PYRROLIDINONE was heated to reflux overnight with stirring. The reaction was allowed to cool and was then poured into 200 mL of water. The aqueous solution was shaken with 200 mL ethyl acetate, the combined aqueous and organic phases were filtered, and the organic phase was separated. The aqueous phase was extracted once more with 200 mL ethyl acetate and the combined organic phases were washed with brine and concentrated. The crude product was chromatographed on silica (5-7% EtOAc- hexane as lutant) to afford 0.505 g (44% yield) of 1, 5-bis- (4-trifluoromethoxy- phenyl)-1 H-indole. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With copper(l) iodide; N,N-dimethylglycine hydrochoride; caesium carbonate; In 1,4-dioxane; at 90℃; | EXAMPLE 11; Step 1; To a solution of 4-(trifluoromethoxy)iodobenzene (0.54 mL, 3.45 mmol), 4-methoxyphenol (0.28 g, 2.26 mmol) and cesium carbonate (1.54 g, 4.73 mmol) in dioxane (10 mL) was added N,N-dimethylglycine hydrochloride (0.03 g, 0.22 mmol). The vessel was purged with nitrogen before Cu(I) iodide (0.02 g, 0.08 mmol) was added. The brownish-green reaction mixture was heated to 90 C. overnight. The reaction mixture was diluted with water and ethyl acetate. The organic portion was washed with brine, dried over anhydrous Na2SO4 and concentrated in vacuo to give the title compound (0.8 g, 100%) as brown oil. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
25% | Preparation of (1S)-N-(2-amino-1-hydroxycarbamoyl-ethyl)-4-(4-trifluoromethoxy- phenylethynyl)-benzamide (5). Resin (3) (120 mg, 0.084 mmol) was swelled in DCM (2 mL) for 1 h and drained. A solution of 4-(trifiuoromethoxy)iodobenzene (4) (96.8 mg, 0.336 mmol) and Et3N (150 μL, 1.10 mmol) in DMF (2.0 mL) was purged with a stream of N2 bubbles for two minutes and added to the resin. After mixing for 5 min, PdCl2(PPh3 )2 (18.0 mg, 0.025 mmol) and CuI (8.0 mg, 0.042 mmol) were added and the mixture shaken for 24 h. The resin was drained, washed with DMF (3x2 mL), DCM (3x2 mL) and cleaved with 10% TFA/DCM (2.0 mL) for 20 min. The solution was collected and the resin was rinsed with additional 10% TFA/DCM (1.0 mL). The cleavage fractions were combined, treated with neat TFA (3.0 mL), stirred for 1 h at rt and concentrated by rotary evaporation to give a crude brown residue. Purification by RP-HPLC (C18 column, CH3CN gradient 5-55%, 0.1% TFA, UV analysis 300 nm, 28 min) and lyophilization of the collected fractions afforded 9.0 mg (25% yield) of (5) as a white solid. LRMS (ES+) m/z 408.0 (C19Hi6F3N3O4+H requires 408.11); RP-HPLC (300 nm, 28 min run) 18.0 min. | |
22% | Resin 3 (120 mg, 0.084 mmol) was swelled in DCM (2 mL) for 1 h and drained. A solution of 4-(trifluoromethoxy)iodobenzene 4 (96.8 mg, 0.336 mmol) and Et3N (150 mL, 1.10 mmol) in DMF (2.0 mL) was purged with a streamof N2 bubbles for two minutes and added to the resin. After mixing for 5 min, PdCl2(PPh3)2 (18.0 mg, 0.025 mmol) andCuI (8.0 mg, 0.042 mmol) were added and the mixture shaken for 24 h. The resin was drained, washed with DMF (3 32 mL), DCM (3 3 2 mL) and cleaved with 10% TFA/DCM (2.0 mL) for 20 min. The solution was collected and the resinwas rinsed with additional 10% TFA/DCM (10 mL). The cleavage fractions were combined, treated with neat TFA (3.0mL), stirred for 1 h at rt and concentrated by rotary evaporation to give a crude brown residue. Purification by RP-HPLC(C18 column, CH3CN gradient 5-55%, 0.1% TFA, UV analysis 300 nm, 28 min) and lyophilization of the collected fractionsafforded 9.0 mg (25% yield) of (1S)-N-(2-amino-1-hydroxycarbamoyl-ethyl)-4-(4-trifluoromethoxy-phenylethynyl)-benzamideas a white solid. LRMS (ES+) m/z 408.0 (C19H16F3N3O4 + H requires 408.11); RP-HPLC (300 nm, 28 min run)18.0 min. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
56% | With copper(l) iodide; 8-quinolinol; caesium carbonate; In water; N,N-dimethyl-formamide; at 130℃; for 17h; | A round bottom flask was charged with 4-bromo-1H-imidazole (3.83 g, 26.0 mmol), copper(I) iodide (0.331 g, 1.736 mmol), quinolin-8-ol (0.252 g, 1.736 mmol), cesium carbonate (11.31 g, 34.7 mmol), and <strong>[103962-05-6]1-iodo-4-(trifluoromethoxy)benzene</strong> (2.72 mL, 17.36 mmol). A 10:1 mixture of DMF (50 mL) and water (5.0 mL) were added to the reaction mixture, and the solution was heated to 130C overnight. After stirring 17 h, LC-MS indicated reaction completion. The reaction mixture was cooled to room temperature, was diluted with EtOAc, and was transferred to a separatory funnel with the aid of water. The layers were separated, and the aqueous layer was extracted with EtOAc. The combined organic layers were washed with saturated aqueous sodium bicarbonate and then ammonium chloride, were dried overNa2SO4/magnesium sulfate (MgSO4) and were concentrated in vacuo. Purification of the residue by normal-phase high-performance liquid chromatography, eluting with 0 - 10% methanol-DCM afforded the title compound as an off-white solid (3.01 g, 56%):1H NMR (400 MHz, CDCl3) d 7.70 (d, J = 1.6 Hz, 1H), 7.41 (d, J = 9.0 Hz, 2H), 7.36 (d, J = 8.9 Hz, 2H), 7.24 (d, J = 1.5 Hz, 1H);19F NMR (376 MHz, CDCl3) d - 58.05; ESIMS m/z 307 ([M+H]+). |
With copper(l) iodide; 8-quinolinol; caesium carbonate; In water; N,N-dimethyl-formamide; at 130℃; for 4h; | Example 19; Preparation of 4-bromo-1-(4-trifluoromethoxyphenyl)-1H-imidazole A round bottom flask was charged with 4-bromoimidazole (1.15 g, 7.81 mmol), CuI (0.07 g, 0.36 mmol), 8-hydroxyquinoline (0.05 g, 0.36 mmol), cesium carbonate (3.39 g, 10.4 mmol) and 4-trifluoromethoxyiodobenzene (1.50 g, 5.21 mmol). A 10:1 mixture of DMF (15 mL) and H2O (1.5 mL) were added to the reaction mixture, and the solution was heated to 130 C. for 4 h. The reaction mixture was then diluted with EtOAc and washed sequentially with water, ammonium chloride (saturated), water and sodium bicarbonate. The organics were dried over MgSO4, filtered and purified on a reverse phase column to give 820 mg of imidazole as a white solid. MS 308.0 (M+H); mp 139-141 C. | |
With copper(l) iodide; 8-quinolinol; caesium carbonate; In water; N,N-dimethyl-formamide; at 130℃; for 4h; | A round bottom flask was charged with 4-bromoimidazole (1.15 g, 7.81 mmol), CuI (0.07 g, 0.36 mmol), 8-hydroxyquinoline (0.05 g, 0.36 mmol), cesium carbonate (3.39 g, 10.4 mmol) and 4-trifluoromethoxyiodobenzene (1.50 g, 5.21 mmol). A 10:1 mixture of DMF (15 mL) and H2O (1.5 mL) was added to the reaction mixture, and the solution was heated to 130 0C for 4 h. The reaction mixture was then diluted with EtOAc and washed sequentially with H2O, ammonium chloride (NH4Cl, saturated), H2O and sodium bicarbonate (NaHCO3). The organics were dried over MgSO4, filtered and purified by reverse phase column chromatography to give the imidazole (820 mg) as a white solid: mp 139-141 0C; ESIMS m/z 308.0 (M+H). |
With 8-quinolinol; caesium carbonate;copper(l) iodide; In water; N,N-dimethyl-formamide; at 130℃; for 4h; | Example 12: Preparation of 4-bromo-l-(4-trifluoromethoxyphenyl)-lH-imidazole. A round bottom flask was charged with 4-bromoimidazole (1.15 g, 7.81 mmol), CuI (0.07 g, 0.36 mmol), 8-hydroxyquinoline (0.05 g, 0.36 mmol), cesium carbonate (3.39 g, 10.4 mmol) and 4-trifluoromethoxyiodobenzene (1.50 g, 5.21 mmol). A 10:1 mixture of DMF (15 mL) and H2O (1.5 mL) was added to the reaction mixture, and the solution was heated to 130 0C for 4 h. The reaction mixture was then diluted with EtOAc and washed sequentially with water, ammonium chloride (saturated), water and sodium bicarbonate. The organics were dried over MgSO4, filtered and purified on a reverse phase column to give the imidazole (820 mg) as a white solid: mp 139-141 0C; ESIMS m/z 308.0 (M+H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
The synthesis was performed following a procedure of Stara, Irena G.; Stary, Ivo; Kollarovic, Adrian; Teply, Filip; Saman, David; Fiedler, Pavel, Coupling reactions of halobenzenes with alkynes. The synthesis of phenylacetylenes and symmetrical or unsymmetrical 1,2-diphenylacetylenes, Collect. Czech. Chem. Commun. (1999), 64(4), 649-672. To a degassed (argon) solution of 178 mg (0.60 mmol) 1-iodo-4-trifluoromethoxy-benzene in 2 ml piperidine was added 29 mg (0.03 mmol) Pd(PPh3)4 and 5 mg (0.03 mmol) CuI. The reaction mixture was stirred at 50 C. for 10 min, then a solution of 152 mg (0.50 mmol) 2-methyl-2-(2-methyl-4-pent-4-ynyloxy-phenoxy)-propionic acid ethyl ester (example 13A]) in 2 ml piperidine was added dropwise within 1 h. During the addition the oil bath was slowly heated to 80 C. starting after 30 min. The reaction mixture was stirred at this temperature for 3 h and then extracted with chilled aqueous 10% KHSO4/Et2O (three times). The organic phases were washed with aqueous 10% NaCl, dried (Na2SO4) and evaporated. Purification by flash-chromatography on silica gel (n-heptane/EtOAc 95:5 to 9:1) yielded 190 mg of the title compound as a light yellow viscous oil. MS: 464.3 (M)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
64% | With sodium hydrogencarbonate;bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; In tetrahydrofuran; water; at 20℃; for 48h;Inert atmosphere; | M. Synthesis of (6S)-6-({1-methyl-3-[4-(trifluoromethoxy)phenyl]-1H-pyrazol-5-yl}methoxy)-2-nitro-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazine (11) by the method of Scheme 8 A solution of 2-(2-propynyloxy)tetrahydro-2H-pyran (69) (0.758 g, 5.41 mmol), CuI (17 mg, 0.09 mmol) and PdCl2(PPh3)2 (0.158 g, 0.023 mmol) in THF (15 mL) was purged with N2. 1-Iodo-4-(trifluoromethoxy)benzene (70) (1.30 g, 4.51 mmol) in THF (10 mL) was added, followed by a solution of methylhydrazine sulfate (1.95 g, 13.5 mmol) and NaHCO3 (2.27 g, 27 mmol) in water (25 mL). The mixture was flushed with carbon monoxide and then stirred at room temperature for 2 days under one atmosphere of carbon monoxide. The resulting mixture was partitioned between CH2Cl2 and water, the CH2Cl2 fraction was dried, and the solvent was evaporated. Column chromatography of the residue on silica gel (eluting with CH2Cl2) gave 1-methyl-5-[tetrahydro-2H-pyran-2-yloxy)methyl]-3-[4-(trifluoromethoxy)phenyl]-1H-pyrazole (71) (1.034 g, 64%) as a brown solid: mp 40-42 C.; 1H NMR (CDCl3) δ 7.78 (d, J=8.8 Hz, 2H), 7.21 (d, J=8.0 Hz, 2H), 6.51 (s, 1H), 4.75 (d, J=12.8 Hz, 1H), 4.69 (t, J=3.3 Hz, 1H), 4.57 (d, J=12.8 Hz, 1H), 3.94 (s, 3H), 3.84-3.91 (m, 1H), 3.53-3.60 (m, 1H), 1.68-1.88 (m, 2H), 1.50-1.66 (m, 4H). APCI MS m/z 357 [M+H]+. |
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