4-bromo-2,6-diethylaniline

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred mixture of 4-bromo-2,6-diethylaniline (13.6 g, 0.06 mol) in distilled water (14 ml) is added concentrated sulphuric acid (14 ml), followed by brief heating to 60° C. for 1 hour until dissolution is complete. The mixture is allowed to cool to room temperature then further cooled to approximately 0° C. in an ice/salt bath. To this slurry is added an aqueous solution of sodium nitrite (4.1 g, 0.059 mol) in distilled water (20 ml) dropwise over 15 minutes, maintaining the temperature below 5° C., followed by additional stirring for 30 minutes. The reaction mixture is allowed to come to room temperature and then a solution of aqueous potassium iodide (29.8 g, 0.18 mol) in distilled water (30 ml) is added dropwise at room temperature. After the addition is complete the solution is briefly heated to 80° C. then allowed to cool to room temperature again. The reaction mixture is extracted with ethyl acetate (150 ml×3) and the organic phase is washed with 1M aqueous hydrochloric acid (75 ml) and aqueous sodium thiosulfate (2×75 ml). The organic phase is dried over anhydrous sodium sulphate and concentrated under reduced pressure. The residue is purified by column chromatography on silica gel to give 4-bromo-2,6-diethyl-1-iodobenzene (19 g) as an orange liquid. to cool to room temperature then further cooled to approximately 0° C. in an ice/salt bath maintaining the temperature below 5° C. to come to room temperature After the addition is briefly heated to 80° C. to cool to room temperature again The reaction mixture is extracted with ethyl acetate (150 ml×3) the organic phase is washed with 1M aqueous hydrochloric acid (75 ml) and aqueous sodium thiosulfate (2×75 ml) The organic phase is dried over anhydrous sodium sulphate concentrated under reduced pressure The residue is purified by column chromatography on silica gel

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: At 0° C., to a stirred solution of commercial 4-bromo-2,6-diethylaniline (10.0 g, 43.9 mmol) in absolute ethanol (219 mL) was added 48% aq. tetrafluoroboric acid (17.2 mL), followed by tert-butyl nitrite (5.7 mL, 48.0 mmol). After 0.5 h, the reaction was poured into ice cold ether (877 mL). The resulting precipitate was washed with cold ether and dried to give 9.39 g (66%) of the title compound. 1H NMR: consistent. The resulting precipitate was washed with cold ether dried

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: At 0° C., to a stirred solution of commercial 4-bromo-2,6-diethylaniline (10.0 g, 43.9 mmol) in absolute ethanol (219 mL) was added 48% aq. tetrafluoroboric acid (17.2 mL), followed by tert-butyl nitrite (5.7 mL, 48.0 mmol). After 0.5 h, the reaction was poured into ice cold ether (877 mL). The resulting precipitate was washed with cold ether and dried to give 9.39 g (66%) of the title compound. 1H NMR: consistent. The resulting precipitate was washed with cold ether dried

反応条件: temp:-5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 20 g of 4-bromo-2,6-diethylaniline, 160 ml of acetic acid, 100 ml of concentrated HCl solution, 30 ml of water and 100 ml of EtOH is cooled to −5° C., a solution of 6.6 g of sodium nitrite in 25 ml of water is added dropwise and the mixture is left stirring at RT for 30 minutes. The reaction mixture is poured into 170 ml of 50% H3PO2 cooled to 0° C. and is left stirring for 2 hours at 0° C. and then for 48 hours at RT. The reaction mixture is extracted with ether, the organic phase is washed with water, with 1N NaOH solution, with water and dried over Na2SO4, and the solvent is evaporated off under vacuum. The residue is chromatographed on silica gel, eluting with cyclohexane. 18 g of the expected product are obtained. the mixture is left cooled to 0° C. is left stirring for 2 hours at 0° C. for 48 hours at RT The reaction mixture is extracted with ether the organic phase is washed with water, with 1N NaOH solution, with water dried over Na2SO4 the solvent is evaporated off under vacuum The residue is chromatographed on silica gel eluting with cyclohexane

反応条件: temp:-5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 20 g of 4-bromo-2,6-diethylaniline, 160 ml of acetic acid, 100 ml of concentrated HCl solution, 30 ml of water and 100 ml of EtOH is cooled to −5° C., a solution of 6.6 g of sodium nitrite in 25 ml of water is added dropwise and the mixture is left stirring at RT for 30 minutes. The reaction mixture is poured into 170 ml of 50% H3PO2 cooled to 0° C. and is left stirring for 2 hours at 0° C. and then for 48 hours at RT. The reaction mixture is extracted with ether, the organic phase is washed with water, with 1N NaOH solution, with water and dried over Na2SO4, and the solvent is evaporated off under vacuum. The residue is chromatographed on silica gel, eluting with cyclohexane. 18 g of the expected product are obtained. the mixture is left cooled to 0° C. is left stirring for 2 hours at 0° C. for 48 hours at RT The reaction mixture is extracted with ether the organic phase is washed with water, with 1N NaOH solution, with water dried over Na2SO4 the solvent is evaporated off under vacuum The residue is chromatographed on silica gel eluting with cyclohexane

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 4-bromo-2,6-diethylaniline (10 g, 44 mmol) in acetonitrile (20 mL) was added dropwise to a solution of I2 (33.4 g, 131.6 mmol), tert-butylnitrite (7.4 mL, 65.8 mmol) in acetonitrile (80 mL), never allowing the internal temperature to exceed 30° C. After stirring 4 h at ambient temperature, Na2SO3 (100 mL, saturated aqueous) was added and stirred for 1 h. The mixture was extracted with hexanes (3×200 mL). The organics were combined, washed with brine, dried over Na2SO4 and concentrated. The crude oil was purified by flash chromatography (100% hexanes) to afford 37A (1.9 g, 13%) as a red oil. 1H NMR (400 MHz, CDCl3) δ ppm 1.20 (t, J=7.45 Hz, 6 H) 2.77 (q, J=7.58 Hz, 4 H) 7.18 (s, 2 H). to exceed 30° C stirred for 1 h The mixture was extracted with hexanes (3×200 mL) washed with brine dried over Na2SO4 concentrated The crude oil was purified by flash chromatography (100% hexanes)

反応条件: temp:-5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 20 g of 4-bromo-2,6-diethylaniline, 160 ml of acetic acid, 100 ml of concentrated HCl solution, 30 ml of water and 100 ml of EtOH is cooled to −5° C., a solution of 6.6 g of sodium nitrite in 25 ml of water is added dropwise and the mixture is left stirring at RT for 30 minutes. The reaction mixture is poured into 170 ml of 50% H3PO2 cooled to 0° C. and is left stirring for 2 hours at 0° C. and then for 48 hours at RT. The reaction mixture is extracted with ether, the organic phase is washed with water, with 1N NaOH solution, with water and dried over Na2SO4, and the solvent is evaporated off under vacuum. The residue is chromatographed on silica gel, eluting with cyclohexane. 18 g of the expected product are obtained. the mixture is left cooled to 0° C. is left stirring for 2 hours at 0° C. for 48 hours at RT The reaction mixture is extracted with ether the organic phase is washed with water, with 1N NaOH solution, with water dried over Na2SO4 the solvent is evaporated off under vacuum The residue is chromatographed on silica gel eluting with cyclohexane

反応条件: temp:-5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 20 g of 4-bromo-2,6-diethylaniline, 160 ml of acetic acid, 100 ml of concentrated HCl solution, 30 ml of water and 100 ml of EtOH is cooled to −5° C., a solution of 6.6 g of sodium nitrite in 25 ml of water is added dropwise and the mixture is left stirring at RT for 30 minutes. The reaction mixture is poured into 170 ml of 50% H3PO2 cooled to 0° C. and is left stirring for 2 hours at 0° C. and then for 48 hours at RT. The reaction mixture is extracted with ether, the organic phase is washed with water, with 1N NaOH solution, with water and dried over Na2SO4, and the solvent is evaporated off under vacuum. The residue is chromatographed on silica gel, eluting with cyclohexane. 18 g of the expected product are obtained. the mixture is left cooled to 0° C. is left stirring for 2 hours at 0° C. for 48 hours at RT The reaction mixture is extracted with ether the organic phase is washed with water, with 1N NaOH solution, with water dried over Na2SO4 the solvent is evaporated off under vacuum The residue is chromatographed on silica gel eluting with cyclohexane

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred mixture of 4-bromo-2,6-diethylaniline (13.6 g, 0.06 mol) in distilled water (14 ml) is added concentrated sulphuric acid (14 ml), followed by brief heating to 60° C. for 1 hour until dissolution is complete. The mixture is allowed to cool to room temperature then further cooled to approximately 0° C. in an ice/salt bath. To this slurry is added an aqueous solution of sodium nitrite (4.1 g, 0.059 mol) in distilled water (20 ml) dropwise over 15 minutes, maintaining the temperature below 5° C., followed by additional stirring for 30 minutes. The reaction mixture is allowed to come to room temperature and then a solution of aqueous potassium iodide (29.8 g, 0.18 mol) in distilled water (30 ml) is added dropwise at room temperature. After the addition is complete the solution is briefly heated to 80° C. then allowed to cool to room temperature again. The reaction mixture is extracted with ethyl acetate (150 ml×3) and the organic phase is washed with 1M aqueous hydrochloric acid (75 ml) and aqueous sodium thiosulfate (2×75 ml). The organic phase is dried over anhydrous sodium sulphate and concentrated under reduced pressure. The residue is purified by column chromatography on silica gel to give 4-bromo-2,6-diethyl-1-iodobenzene (19 g) as an orange liquid. to cool to room temperature then further cooled to approximately 0° C. in an ice/salt bath maintaining the temperature below 5° C. to come to room temperature After the addition is briefly heated to 80° C. to cool to room temperature again The reaction mixture is extracted with ethyl acetate (150 ml×3) the organic phase is washed with 1M aqueous hydrochloric acid (75 ml) and aqueous sodium thiosulfate (2×75 ml) The organic phase is dried over anhydrous sodium sulphate concentrated under reduced pressure The residue is purified by column chromatography on silica gel

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 4-bromo-2,6-diethylaniline (5.48 g, 24 mmol) in dichloromethane was added and stirred under nitrogen. Pyridine (5.7 g, 72.1 mmol) was added followed by benzoyl chloride (4.39 g, 31.2 mmol). The reaction was stirred for 1 h. The reaction was diluted with dichloromethane, washed with 10% sodium hydroxide solution, 1N HCl, and dried over magnesium sulfate, filtered, and evaporated. The residue was pre-absorbed onto Celite and purified by column chromatography. The column was eluted with 40 to 100% dichloromethane/hexanes. 7.64 g (96% yield) of product was obtained after purification. The reaction was stirred for 1 h washed with 10% sodium hydroxide solution, 1N HCl dried over magnesium sulfate filtered evaporated The residue was pre-absorbed onto Celite purified by column chromatography The column was eluted with 40 to 100% dichloromethane/hexanes

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2,6-diethylaniline (7 g, 46.9 mmol) was dissolved in 50 mL of DMF in a round-bottom flask and cooled with an ice-water bath. N-bromosuccimide (NBS) (9.18 g, 51.6 mmol) was dissolved in 100 mL of DMF and added dropwise to the flask via a dropping funnel. The reaction was warmed slowly to room temperature and reacted overnight before it was quenched by ice water. The product was extracted with dichloromethane and washed with lithium chloride solution. After evaporating solvent, the residue was purified by silica gel column chromatography. 5.5 g (51.4% yield) of product was obtained. cooled with an ice-water bath added dropwise to the flask via a dropping funnel reacted overnight before it was quenched by ice water The product was extracted with dichloromethane washed with lithium chloride solution After evaporating solvent the residue was purified by silica gel column chromatography

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred solution of 2,6-diethylaniline (10.0 g, 67.0 mmol) in acetic acid (50 mL) at ambient temperature was added bromine (10.4 mL, 201 mmol). The reaction was stirred overnight at ambient temperature. The reaction mixture was diluted with diethyl ether (200 mL) and washed with 5% sodium bisulfite (4×50 mL) and brine. The organic phase was dried with sodium sulfate and the solvents were removed in vacuo. The residue was chromatographed on silica gel, eluting with 9:1 hexane-ethyl acetate to give the title compound (3.28 g, 21 % yield). washed with 5% sodium bisulfite (4×50 mL) and brine The organic phase was dried with sodium sulfate the solvents were removed in vacuo The residue was chromatographed on silica gel eluting with 9:1 hexane-ethyl acetate