2-bromo-4-propan-2-ylaniline

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 500 ml round bottom flask was charged with 12.2 grams (65.4 mmol) of 2-cyanophenylboronic acid propanediol ester, 14.0 g (65.4 mmol) of 2-bromo-4-isopropylaniline, 2.27 (2 mmol) tetrakis(triphenylphosphine)palladium, 18.0 g (131 mmol) of potassium carbonate, 150 ml toluene, and 50 ml ethanol. The reaction was heated to reflux under N2 for 18 hours. After cooling to room temperature the reaction was extracted with ethyl acetate and water. The organic was washed with brine and then dried with magnesium sulfate. The solids were collected by filtration and the solvent removed from filtrate. The product was purified by silica gel chromatography using 94.5% dichloromethane, 5% methanol, 0.5% ammonium hydroxide as the eluent. The fractions containing the desired product were combined and the solvent removed. The product was confirmed by NMR and mass spectroscopy. The reaction was heated to reflux under N2 for 18 hours was extracted with ethyl acetate and water The organic was washed with brine dried with magnesium sulfate The solids were collected by filtration the solvent removed from filtrate The product was purified by silica gel chromatography The fractions containing the desired product the solvent removed

Conditions: temp:-5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a mixture of 1000 ml of 96% ethanol and 94 ml of 98% H2SO4, 117 g (0.55 mol) of 2-bromo-4-isopropylaniline was added, while vigorously stirring, at −5° C. over 15 min. Then, a solution of 63 g of NaNO2 in 125 ml of water was added at this temperature over 1 h, and the resulting mixture was stirred for about 30 min longer. Then, 12 g of copper powder was added. The reaction mixture was refluxed for 4 h and then filtered through a glass frit (G3). The filtrate was poured into 2500 cm3 of cold water. The organic product was extracted with 4×400 ml of dichloromethane. The combined extract was dried over K2CO3 and evaporated to dryness. Fractional distillation gave the title product, b.p. 64-67° C./3 mm Hg. Yield 117.4 g (75%) of yellowish oil. was added the resulting mixture was stirred for about 30 min longer The reaction mixture was refluxed for 4 h filtered through a glass frit (G3) The filtrate was poured into 2500 cm3 of cold water The organic product was extracted with 4×400 ml of dichloromethane The combined extract was dried over K2CO3 evaporated to dryness Fractional distillation

Conditions: temp:-5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a mixture of 1000 ml of 96% ethanol and 94 ml of 98% H2SO4, 117 g (0.55 mol) of 2-bromo-4-isopropylaniline was added, while vigorously stirring, at −5° C. over 15 min. Then, a solution of 63 g of NaNO2 in 125 ml of water was added at this temperature over 1 h, and the resulting mixture was stirred for about 30 min longer. Then, 12 g of copper powder was added. The reaction mixture was refluxed for 4 h and then filtered through a glass frit (G3). The filtrate was poured into 2500 cm3 of cold water. The organic product was extracted with 4×400 ml of dichloromethane. The combined extract was dried over K2CO3 and evaporated to dryness. Fractional distillation gave the title product, b.p. 64-67° C./3 mm Hg. Yield 117.4 g (75%) of yellowish oil. was added the resulting mixture was stirred for about 30 min longer The reaction mixture was refluxed for 4 h filtered through a glass frit (G3) The filtrate was poured into 2500 cm3 of cold water The organic product was extracted with 4×400 ml of dichloromethane The combined extract was dried over K2CO3 evaporated to dryness Fractional distillation

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 99 g (0.73 mol) of 4-isopropylaniline (Acros) and 300 ml of acetic acid was refluxed for 1 h; then, 75 g of acetic anhydride was added dropwise while vigorously stirring. The resulting solution was cooled to 50° C., and 37.4 ml of bromine was added dropwise, while vigorously stirring, over ca. 30 min. Then, 370 ml of 12 M HCl was added and this mixture was refluxed until a precipitate was formed. This precipitate was separated, washed with 2×150 ml of methyl-tert-butyl ether, and dried in vacuum. A mixture of the solid obtained and a solution of 112 g of KOH in 300 ml of water was stirred at 50-60° C. for 1 h. The organic layer was separated, and the aqueous layer was extracted with 2×150 ml of methyl-tert-butyl ether. The combined extract was dried over K2CO3 and evaporated to dryness. Fractional distillation gave the title product, b.p. 107-111° C./3 mm Hg. Yield 83.7 g (77%) of yellowish oil. was refluxed for 1 h while vigorously stirring, over ca. 30 min this mixture was refluxed until a precipitate was formed This precipitate was separated washed with 2×150 ml of methyl-tert-butyl ether dried in vacuum A mixture of the solid obtained The organic layer was separated the aqueous layer was extracted with 2×150 ml of methyl-tert-butyl ether The combined extract was dried over K2CO3 evaporated to dryness Fractional distillation

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 99 g (0.73 mol) of 4-isopropylaniline (Acros) and 300 ml of acetic acid was refluxed for 1 h; then, 75 g of acetic anhydride was added dropwise while vigorously stirring. The resulting solution was cooled to 50° C., and 37.4 ml of bromine was added dropwise, while vigorously stirring, over ca. 30 min. Then, 370 ml of 12 M HCl was added and this mixture was refluxed until a precipitate was formed. This precipitate was separated, washed with 2×150 ml of methyl-tert-butyl ether, and dried in vacuum. A mixture of the solid obtained and a solution of 112 g of KOH in 300 ml of water was stirred at 50-60° C. for 1 h. The organic layer was separated, and the aqueous layer was extracted with 2×150 ml of methyl-tert-butyl ether. The combined extract was dried over K2CO3 and evaporated to dryness. Fractional distillation gave the title product, b.p. 107-111° C./3 mm Hg. Yield 83.7 g (77%) of yellowish oil. was refluxed for 1 h while vigorously stirring, over ca. 30 min this mixture was refluxed until a precipitate was formed This precipitate was separated washed with 2×150 ml of methyl-tert-butyl ether dried in vacuum A mixture of the solid obtained The organic layer was separated the aqueous layer was extracted with 2×150 ml of methyl-tert-butyl ether The combined extract was dried over K2CO3 evaporated to dryness Fractional distillation

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 500 ml round bottom flask was charged with 12.2 grams (65.4 mmol) of 2-cyanophenylboronic acid propanediol ester, 14.0 g (65.4 mmol) of 2-bromo-4-isopropylaniline, 2.27 (2 mmol) tetrakis(triphenylphosphine)palladium, 18.0 g (131 mmol) of potassium carbonate, 150 ml toluene, and 50 ml ethanol. The reaction was heated to reflux under N2 for 18 hours. After cooling to room temperature the reaction was extracted with ethyl acetate and water. The organic was washed with brine and then dried with magnesium sulfate. The solids were collected by filtration and the solvent removed from filtrate. The product was purified by silica gel chromatography using 94.5% dichloromethane, 5% methanol, 0.5% ammonium hydroxide as the eluent. The fractions containing the desired product were combined and the solvent removed. The product was confirmed by NMR and mass spectroscopy. The reaction was heated to reflux under N2 for 18 hours was extracted with ethyl acetate and water The organic was washed with brine dried with magnesium sulfate The solids were collected by filtration the solvent removed from filtrate The product was purified by silica gel chromatography The fractions containing the desired product the solvent removed

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 500 ml round bottom flask was charged with 12.2 grams (65.4 mmol) of 2-cyanophenylboronic acid propanediol ester, 14.0 g (65.4 mmol) of 2-bromo-4-isopropylaniline, 2.27 (2 mmol) tetrakis(triphenylphosphine)palladium, 18.0 g (131 mmol) of potassium carbonate, 150 ml toluene, and 50 ml ethanol. The reaction was heated to reflux under N2 for 18 hours. After cooling to room temperature the reaction was extracted with ethyl acetate and water. The organic was washed with brine and then dried with magnesium sulfate. The solids were collected by filtration and the solvent removed from filtrate. The product was purified by silica gel chromatography using 94.5% dichloromethane, 5% methanol, 0.5% ammonium hydroxide as the eluent. The fractions containing the desired product were combined and the solvent removed. The product was confirmed by NMR and mass spectroscopy. The reaction was heated to reflux under N2 for 18 hours was extracted with ethyl acetate and water The organic was washed with brine dried with magnesium sulfate The solids were collected by filtration the solvent removed from filtrate The product was purified by silica gel chromatography The fractions containing the desired product the solvent removed