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CAS No. : | 144649-99-0 | MDL No. : | MFCD00143429 |
Formula : | C8H6BrNO | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | LOASAXVECBZCRJ-UHFFFAOYSA-N |
M.W : | 212.04 | Pubchem ID : | 4418560 |
Synonyms : |
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Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P264-P270-P271-P280-P301+P312+P330-P302+P352+P312-P304+P340+P312-P305+P351+P338-P337+P313-P501 | UN#: | N/A |
Hazard Statements: | H302-H312-H332-H320 | Packing Group: | N/A |
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 |
---|---|---|
90% | Example 58 3-(4.6-Diamino-[1,3,5]triazin-2-yl)-biphenyl-4,4'-diol One equivalent of 5-bromo-2-methoxy-benznitrile (1 mmol) was reacted with 4-methoxyphenylboronic acid (1.05 mmol), following General Procedure G, to give 4,4'-dimethoxy-3-cyanobiphenol in 90percent yield. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | With formic acid; hydroxylamine hydrochloride; sodium acetate; for 15h;Reflux; | 5-Bromo-2-methoxybenzaldehyde (20.00 mmol, 4.30 g) was dissolved in formic acid (20 mL) and treated with hydroxylamine hydrochloride (21.00 mmol, 1.45 g) and sodium acetate (26.00 mmol, 2.13 g). The reaction mixture was heated at reflux for 15 hours. The solvent was removed under reduced pressure and the residue was taken up in ethyl acetate (250 mL). The organics were washed with saturated sodium bicarbonate solution (2.x.200 mL) and then dried with MgSO4. The organics were filtered and evaporated under reduced pressure to yield the title compound as a white solid. Yield=4.10 g, 97percent. Analytical LCMS method 2, retention time 6.07 min, M+H=214, 216. 1H NMR: (CDCl3) delta: 7.66-7.61 (m, 2H), 6.87 (d, 1H), 3.92 (s, 3H). |
With sodium hydroxide; formic acid; hydroxylamine hydrochloride; sodium formate; | EXAMPLE I A mixture of 6.45 g 5-bromo-o-anisaldehyde, 2.2 g of hydroxylamine hydrochloride, 4.1 g of sodium formate and 20 mL formic acid were heated at 100° C. with stirring for 1 h. The reaction mixture was poured onto ice water and the mixture was made basic by the careful addition of 50percent sodium hydroxide. The product was extracted with ether, the ether extracts were dried over magnesium sulfate and the solvent was removed in vacuo. The residue was crystallized from ether/hexane to afford 5-bromo-2-methoxybenzonitrile. | |
With sodium hydroxide; hydroxylamine hydrochloride; sodium acetate; acetic anhydride; acetic acid; | EXAMPLE I STR31 A mixture of 5-Bromo-o-anisaldehyde (6.45 g), hydroxylamine hydrochloride (2.2 g), sodium acetate (4.1 g) and acetic acid (20 mL) was heated at 100° C. with stirring for 1 h. Acetic anhydride was added (20 mL) and the mixture was refluxed for 8 h. The reaction mixture was poured onto ice water and the mixture was made basic by the careful addition of 50percent sodium hydroxide. The product was extracted with ether, the ether extracts were dried over magnesium sulfate and the solvent was removed in vacuo. The residue was crystallized from ether/hexane to afford 5-Bromo-2-methoxy-benzonitrile. |
With sodium hydroxide; hydroxylamine hydrochloride; sodium acetate; acetic anhydride; acetic acid; | EXAMPLE I STR21 A mixture of 5-Bromo-o-anisaldehyde (6.45 g), hydroxylamine hydrochloride (2.2 g), sodium acetate (4.1 g) and acetic acid (20 mL) was heated at 100° C. with stirring for 1 h. Acetic anhydride was added (20 mL) and the mixture was refluxed for 8 h. The reaction mixture was poured onto ice water and the mixture was made basic by the careful addition of 50percent sodium hydroxide. The product was extracted with ether, the ether extracts were dried over magnesium sulfate and the sovent was removed in vacuo. The residue was crystallized from ether/hexane to afford 5-Bromo-2-methoxybenzonitrile. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
16.23 ml of n-butyllithium solution (1.6M in hexane) are added dropwise to a solution of 5.00 g of <strong>[144649-99-0]5-bromo-2-methoxybenzonitrile</strong> in 90 ml of dry tetrahydrofuran at -78°C. After stirring at this temperature for 45 minutes, 6.71 ml of triisopropylborate are added, and the mixture is then slowly warmed to -20°C. 50 ml of 1 N HCl are added to the reaction mixture. The phase is separated and the aqueous phase is extracted three more times with 100 ml of diethyl ether each time. The combined organic phases are dried with sodium sulphate, filtered and evaporated. The remaining oil is mixed with pentane, and the precipitate which separates out is filtered off with suction and washed once with a little dichloromethane. Drying under high vacuum affords the title compound as a white solid. Rt = 2.74. | ||
16.23 ml of n-butyllithium solution (1.6M in hexane) are added dropwise to a solution of 5.00 g of <strong>[144649-99-0]5-bromo-2-methoxybenzonitrile</strong> in 90 ml of dry tetrahydrofuran at -78° C. After stirring at this temperature for 45 minutes, 6.71 ml of triisopropylborate are added, and the mixture is then slowly warmed to -20° C. 50 ml of 1N HCl are added to the reaction mixture. The phase is separated and the aqueous phase is extracted three more times with 100 ml of diethyl ether each time. The combihled organic phases are dried with sodium sulphate, filtered and evaporated. The remaining oil is mixed with pentane, and the precipitate which separates out is filtered off with suction and washed once with a little dichloromethane. Drying under high vacuum affords the title compound as a white solid. Rt=2.74. | ||
16.23 ml of n-butyllithium solution (1.6M in hexane) are added dropwise to a solution of 5.00 g of <strong>[144649-99-0]5-bromo-2-methoxybenzonitrile</strong> in 90 ml of dry tetrahydrofuran at -78°C. After stirring at this temperature for 45 minutes, 6.71 ml of triisopropylborate are added, and the mixture is then slowly warmed to -200C. 50 ml of 1 N HCI are added to the reaction mixture. The phase is separated and the aqueous phase is extracted three more times with 100 ml of diethyl ether each time. The combined organic phases are dried with sodium sulphate, filtered and evaporated. The remaining oil is mixed with pentane, and the precipitate which separates out is filtered off with suction and washed once with a little dichloromethane. Drying under high vacuum affords the title compound as a white solid. Rt = 2.74. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
27% | With sodium tetrahydroborate; nickel dichloride; In ethanol; at 0 - 20℃; for 3h; | Example 38 1,1-Dimethylethyl [5-bromo-2-(methyloxy)phenyl]methyl}carbamate NaBH4 (2.9 g, 75.5 mmol) was cautiously added in several portions to a solution of NiCl2 (2.6 g, 19.8 mmol), Boc2O (8.2 g, 37.7 mmol) and <strong>[144649-99-0]5-bromo-2-(methyloxy)benzonitrile</strong> (4.0 g, 18.9 mmol) in dry EtOH (70 mL) at 0° C. Once the reaction had subsided, the mixture was left to stir at room temperature for 3 h. Ethanol was removed under reduced pressure and the residue was dissolved in EtOAc and saturated solution of NaHCO3, then filtered and repeatedly washed with EtOAc. The combined organic phases were dried using Na2SO4. The crude product was purified by flash column chromatography (PE/EA=20:1) to give 1.6 g of the product, 1,1-dimethylethyl [5-bromo-2-(methyloxy)phenyl]methyl}-carbamate. (Yield: 27percent). 1H NMR (400 MHz, CDCl3): delta 7.36-7.33 (m, 2H), 6.74 (d, J=8.8 Hz, 1H), 4.97 (br, 1H), 4.27 (d, J=4.8 Hz, 1H), 3.82 (s, 3H), 1.45 (s, 9H); 13C NMR (400 MHz, CDCl3): delta 156.5, 155.8, 131.7, 131.1, 129.3, 111.8, 79.5, 55.5, 39.9, 26.4. HPLC: retention time: 6.592 min; purity: 97.9percent. |
25% | With sodium tetrahydroborate; ethanol;nickel dichloride; at 0 - 20℃; | Example 35 1,1-Dimethylethyl[5-bromo-2-(methyloxy)phenyl]methyl}carbamate NaBH4 (2.9 g, 75.5 mmol) was cautiously added in several portions to a solution of NiCl2 (2.6 g, 19.8 mmol), Boc2O (8.2 g, 37.7 mmol) and <strong>[144649-99-0]5-bromo-2-(methyloxy)benzonitrile</strong> (4.0 g, 18.9 mmol) in dry EtOH (70 mL) at 0° C. Once the reaction had subsided, the mixture was left to stir at room temperature for 3 h. Ethanol was removed under reduced pressure and the residue was dissolved in EtOAc and saturated solution of NaHCO3, then filtered and the aqueous layer was repeatedly washed with EtOAc. The combined organic phases were dried Na2SO4. The crude product was purified by flash column chromatography to give the captioned the product (1.5 g yield: 25percent). 1H NMR (400 MHz, CDCl3) delta 7.36-7.33 (m, 2H), 6.74 (d, J=8.8 Hz, 1H), 4.97 (br, 1H), 4.27 (d, J=4.8 Hz, 1H), 3.82 (s, 3H), 1.45 (s, 9H); 13C NMR (400 MHz, CDCl3) delta 156.5, 155.8, 131.7, 131.1, 129.3, 111.8, 79.5, 55.5, 39.9, 26.4. HPLC: retention time. |
25% | With sodium tetrahydroborate; ethanol; nickel dichloride; at 0 - 20℃; for 3h; | Example 35 1,1-Dimethylethyl [5-bromo-2-(methyloxy)phenyl] methyl} carbamateNaBH4 (2.9 g, 75.5 mmol) was cautiously added in several portions to a solution OfNiCl2 (2.6 g, 19.8 mmol), BoC2O (8.2 g, 37.7 mmol) and <strong>[144649-99-0]5-bromo-2-(methyloxy)benzonitrile</strong> (4.0 g, 18.9 mmol) in dry EtOH (70 mL) at 0 0C. Once the reaction had subsided, the mixture was left to stir at room temperature for 3 h. Ethanol was removed under reduced pressure and the residue was dissolved in EtOAc and saturated solution of NaHCpsi3, then filtered and the aqueous layer was repeatedly washed with EtOAc. The combined organic phases were dried Na2SO4. The crude product was purified by flash column chromatography to give the captioned the product (1.5g yield: 25percent). 1H NMR (400 MHz, CDCl3) delta 7.36-7.33 (m, 2 H), 6.74 (d, J=8.8 Hz, 1 H), 4.97 (br, 1 H), 4.27(d, J=4.8 Hz, 1 H), 3.82 (s, 3 H), 1.45 (s, 9 H); 13C NMR (400 MHz, CDCl3) delta 156.5, 155.8, 131.7, 131.1, 129.3, 111.8, 79.5, 55.5, 39.9, 26.4. HPLC: retention time. |
With sodium tetrahydroborate; nickel dichloride; In ethanol; at 0 - 20℃; | Example 35 1,1-Dimethylethyl [5-bromo-2-(methyloxy)phenyl]methyl}carbamate NaBH4 (2.9 g, 75.5 mmol) was cautiously added in several portions to a solution of NiCl2 (2.6 g, 19.8 mmol), Boc2O (8.2 g, 37.7 mmol) and <strong>[144649-99-0]5-bromo-2-(methyloxy)benzonitrile</strong> (4.0 g, 18.9 mmol) in dry EtOH (70 mL) at 0° C. Once the reaction had subsided, the mixture was left to stir at room temperature for 3 h. Ethanol was removed under reduced pressure and the residue was dissolved in EtOAc and saturated solution of NaHCO3, then filtered and the aqueous layer was repeatedly washed with EtOAc. The combined organic phases were dried Na2SO4. The crude product was purified by flash column chromatography to give the captioned the product (1.5 g yield: 25percent). 1H NMR (400 MHz, CDCl3) delta 7.36-7.33 (m, 2H), 6.74 (d, J=8.8 Hz, 1H), 4.97 (br, 1H), 4.27 (d, J=4.8 Hz, 1H), 3.82 (s, 3H), 1.45 (s, 9H); 13C NMR (400 MHz, CDCl3) delta 156.5, 155.8, 131.7, 131.1, 129.3, 111.8, 79.5, 55.5, 39.9, 26.4. HPLC: retention time. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With N-Bromosuccinimide; iodine; In acetonitrile; for 12h;Darkness; | General procedure: To a reaction tube charged with NBS (1.5 equiv, 0.3 mmol), catalyst (10 molpercent, 0.02 mmol) and CH3CN (1.0 mL),was added para-chloroanisole 1a (0.2 mmol). After being stirred at room temperature for 12 h in dark, the reaction was quenched by saturated aq. solution of Na2S2O3 (2 mL). The resulting mixture was extracted by ethyl acetate (3 5 mL). The combined organic extracts were washed by brine (10 mL), dried over Na2SO4 and filtered through a pad of Celite. The filtrate was concentrated under reduced pressure and the residuewas purified by flash chromatography on a silica gel column with petroleum ether/dichloromethane (5:1) as the eluent to give 4.3.1. 2-Bromo-4-chloroanisole (2a) |
71% | With bromine; In chloroform; for 29h;Reflux; | Example 34 5-Bromo-2-(methyloxy)benzonitrile Br2 (13.7 g, 86.0 mmol) in CHCl3 (20 mL) was added to a solution of 2-(methyloxy)benzonitrile (10.9 g, 81.9 mmol) in CHCl3 (50 mL). The mixture was refluxed for 29 h. The reaction was allowed to cool to room temperature, and washed with saturated sodium bisulfite (50 mL), and brine (50 mL). The organic layer was dried over anhydrous sodium sulfate. Evaporation of the solvent afforded 5-bromo-2-(methyloxy)benzonitrile (12.4 g, 71percent). |
71% | With bromine; In chloroform; for 29h;Reflux; | Example 34 5-Bromo-2-(methyloxy)benzonitrile Bromine (13.7 g, 86.0 mmol) in CHCl3 (20 mL) was added to a solution of 2-(methyloxy)benzonitrile (10.9 g, 81.9 mmol) in CHCl3 (50 mL). The mixture was refluxed for 29 h. The reaction was allowed to cool to room temperature, and washed with saturated sodium bisulfite (50 mL), and brine (50 mL). The organic layer was dried over anhydrous sodium sulfate. Evaporation of the solvent afforded 5-bromo-2-(methyloxy)benzonitrile (12.4 g, 71percent). |
71% | With bromine; In chloroform; for 29h;Heating; | Example 37 5-Bromo-2-(methyloxy)benzonitrile Bromine (13.7 g, 86.0 mmol) in CHCl3 (20 mL) was added to the solution of 2-(methyloxy)benzonitrile (10.9 g, 81.9 mmol) in CHCl3 (50 mL). The mixture was refluxed for 29 h. The reaction was allowed to cool to room temperature, and washed with saturated sodium bisulfite (50 mL), and brine (50 mL). The organic layer was dried over anhydrous sodium sulfate. Evaporation of the solvent afforded 5-bromo-2-(methyloxy)benzonitrile (12.4 g, 71percent). |
71% | With bromine; In chloroform; for 29h;Reflux; | Example 34 5-Bromo-2-(methyloxy)benzonitrile <n="134"/>Br2 (13.7 g, 86.0 mmol) in CHCl3 (20 mL) was added to a solution of 2-(methyloxy)benzonitrile (10.9 g, 81.9 mmol) in CHCl3 (50 mL). The mixture was refluxed for 29 h. The reaction was allowed to cool to room temperature, and washed with saturated sodium bisulfite (50 mL), and brine (50 mL). The organic layer was dried over anhydrous sodium sulfate. Evaporation of the solvent afforded 5-bromo-2-(methyloxy)benzonitrile (12.4 g, 71percent). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
63% | <strong>[144649-99-0]5-Bromo-2-methoxy-benzonitrile</strong> (25.00 mmol, 5.73 g) was dissolved in ethanol (35 mL) and treated with ethyl propiolate (28.75 mmol, 2.93 g). The reaction mixture was heated at 60° C. for 30 minutes and then treated with a solution of potassium hydroxide (28.75 mmol, 1.63 g) in ethanol (35 mL). The reaction mixture was then heated at reflux for 3 hours and then allowed to cool to room temperature. The reaction mixture was concentrated under reduced pressure and taken up in water 300 mL. The mixture was adjusted to pH 4 with conc hydrochloric acid and the resultant solid was filtered off and washed with water. The solid was transferred to a round bottom flask, suspended in toluene and evaporated to dryness twice to provide the title compound as an off white solid. Yield=4.4 g, 63percent. Analytical LCMS method 2, retention time 4.28 min, M+H=281. 1H NMR: (CDCl3) delta: 11.0 (br, s, 1H), 8.57 (d, 1H), 8.04 (d, 1H), 7.61 (dd, 1H), 6.95 (d, 1H), 6.37 (d, 1H), 4.04 (s, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With potassium acetate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In 1,4-dioxane; at 80℃; for 18h; | 2-Methoxy-5-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)benzonitrile: To a solution of <strong>[144649-99-0]2-methoxy-5-bromobenzonitrile</strong> (5.0 g, 23.6 mmol) in /?-dioxane (125 mL), bis(pinacolato)diborane (9.0 g, 35.4 mmol), KOAc ( 7.0 g, 71.3 mmol), and Pd(dppf)Cl2 ( 0.863 g, 1.17 mmol) were added. The resulting mixture was stirred for 18 h at 80 °C. The cooled reaction crude was diluted with 1200 mL EtOAc, washed with H20 and brine, dried (Na2S04), filtered, and concentrated in vacuo. The residue was purified by column chromatography on Si02 (Hexanes/EtOAc) to afford the title compound (5.6 g, 92percent). |
92% | With potassium acetate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In 1,4-dioxane; at 80℃; for 18h; | Preparation of Intermediate 1-2; 5-(2-Chloropyrimidin-4-yl)-2-methoxybenzonitrileReagents: (a) Pd(dppf)Cl2, KOAc, /?-dioxane: (b) 2,4-dichloropyrimidine, K2C03,Pd(PPh3)4, CH3CN, H20, reflux, 5 h;[0209] Step 1. 2-Methoxy-5-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)benzonitrile: To a solution of <strong>[144649-99-0]2-methoxy-5-bromobenzonitrile</strong> (5.0 g, 23.6 mmol) in /?-dioxane (125 mL), bis(pinacolato)diborane (9.0 g, 35.4 mmol), KOAc (7.0 g, 71.3 mmol), and Pd(dppf)Cl2 (0.863 g, 1.17 mmol) were added. The resulting mixture was stirred for 18 h at 80 °C. The cooled reaction crude was diluted with 120 mL EtOAc, washed with H20 and brine, dried (Na2S04), filtered, and concentrated in vacuo. The residue was purified by column chromatography on Si02 (Hexanes/EtOAc) to afford the title compound (5.6 g, 92percent). GC/MS (EI, M+) 245 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
47.6% | With caesium carbonate;palladium diacetate; XPhos; In toluene; at 120℃; for 50h;Inert atmosphere; | Intermediate 52f: (i?)-5-(2-(tert-Butyldimethylsilyloxy)propylamino)-2- methoxybenzonitrile Pd(OAc)2 (0.529 g, 2.36 mmol) and dicyclohexyl(2',4',6'-triisopropylbiphenyl-2- yl)phosphine (1.124 g, 2.36 mmol) were added in one portion to a degassed solution of 5- bromo-2-methoxybenzonitrile (5 g, 23.58 mmol), (R)-2-(tert- butyldimethylsilyloxy)propan-l -amine (Intermediate 48g; 5.36 g, 28.30 mmol) and cesium carbonate (11.52 g, 35.37 mmol) in toluene (100 mL) at 20°C under nitrogen. The resulting suspension was stirred at 120 °C for 50 hours. The reaction mixture was diluted with EtOAc (150 mL) and water (150 mL) and the biphasic mixture was filtered through celite. The organic layer was separated and washed sequentially with water (150 mL) and saturated brine (150 mL). The organic layer was evaporated to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 0 to 20percent> EtOAc in isohexane. Pure fractions were evaporated to dryness to afford the title compound (3.60 g, 47.6 percent) as a pale yellow oil. 1H NMR (400 MHz, CDC13) 0.05 (3H, s), 0.07 (3H, s), 0.90 (9H, s), 1.21 (3H, d), 2.87 - 2.97 (1H, m), 3.09 (1H, d), 3.85 (3H, s), 3.99 - 4.07 (1H, m), 6.69 - 6.91 (3H, m), 7.63 - 7.69 (1H, m). m/z (ES+) (M+H)+ = 321.38 |