4-Bromo-2,5-dimethylaniline

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: 373 g of 2-amino-5-bromo-p-xylene were suspended in 1860 ml of H2O in a 4 l four-necked flask, the mixture was cooled to 3° C. (internal temperature), and 612 ml of tetrafluoroboric acid were added. 154 g of NaNO2 in 300 ml of water were then added dropwise over the course of 60 minutes. After 60 minutes, the solid was filtered off with suction and washed with a little cold 5% tetrafluoroboric acid, then with a little cold methanol and finally with a little cold diethyl ether. The yellow solid (497 g=90%) was dried overnight in an oil-pump vacuum. were added the solid was filtered off with suction washed with a little cold 5% tetrafluoroboric acid The yellow solid (497 g=90%) was dried overnight in an oil-pump vacuum

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

Procedure: 373 g of 2-amino-5-bromo-p-xylene were suspended in 1860 ml of H2O in a 4 l four-necked flask, the mixture was cooled to 3° C. (internal temperature), and 612 ml of tetrafluoroboric acid were added. 154 g of NaNO2 in 300 ml of water were then added dropwise over the course of 60 minutes. After 60 minutes, the solid was filtered off with suction and washed with a little cold 5% tetrafluoroboric acid, then with a little cold methanol and finally with a little cold diethyl ether. The yellow solid (497 g=90%) was dried overnight in an oil-pump vacuum. were added the solid was filtered off with suction washed with a little cold 5% tetrafluoroboric acid The yellow solid (497 g=90%) was dried overnight in an oil-pump vacuum

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

Procedure: 316 g of 2-bromo-5-nitro-p-xylene were dissolved in 3000 ml of methanol, freshly produced Raney nickel (about 4 g) was added under a vigorous stream of N2, and the mixture was heated to reflux with vigorous stirring. 275 ml of hydrazine hydrate (80% in water) were then slowly added dropwise. When the dropwise addition was complete (duration about 5 hours), the mixture was refluxed for about a further 6 hours. The catalyst was filtered off, the methanol was removed in a rotary evaporator, the residue was taken up in ethyl acetate, and the solution was washed by shaking with water, dried and re-evaporated in a rotary evaporator. The resultant crude product was recrystallized from heptane, giving 238 g (87%) of pale-green crystals. the mixture was heated to reflux with vigorous stirring When the dropwise addition the mixture was refluxed for about a further 6 hours The catalyst was filtered off the methanol was removed in a rotary evaporator the solution was washed dried re-evaporated in a rotary evaporator The resultant crude product was recrystallized from heptane

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

Procedure: A suspension of 4-bromo-2,5-dimethylaniline (4.00 g, 20 mmol), pyridin-3-ylboronic acid (2.70 g, 11 mmol), Pd2(dba)3 (0.55 g, 0.6 mmol), 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (0.98 g, 1.2 mmol) and Na2CO3 (10.6 g, 100 mmol) in n-BuOH (50 mL) was degassed by a stream of argon gas for 15 min. The reaction flask was sealed and placed in a pre-heated oil bath (115° C.). After stirring overnight, the reaction was cooled and filtered. The filter cake was washed with DCM and the filtrate was concentrated in vacuo. The resulting residue was dissolved in EtOAc (150 mL). EtOAC was sequentially washed with water (20 mL), brine (20 mL), dried over Na2SO4 and evaporated. The crude product was purified by silica chromatography (0-50% EtOAC in hexanes gradient) to give 2,5-dimethyl-4-(pyridin-3-yl)aniline as a yellow solid; ESMS m/z 199.1 (M+H+). was degassed by a stream of argon gas for 15 min The reaction flask was sealed placed in a pre-heated oil bath (115° C.) the reaction was cooled filtered The filter cake was washed with DCM the filtrate was concentrated in vacuo The resulting residue was dissolved in EtOAc (150 mL) EtOAC was sequentially washed with water (20 mL), brine (20 mL) dried over Na2SO4 evaporated The crude product was purified by silica chromatography (0-50% EtOAC in hexanes gradient)

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

Procedure: A suspension of 4-bromo-2,5-dimethylaniline (4.00 g, 20 mmol), pyridin-3-ylboronic acid (2.70 g, 11 mmol), Pd2(dba)3 (0.55 g, 0.6 mmol), 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (0.98 g, 1.2 mmol) and Na2CO3 (10.6 g, 100 mmol) in n-BuOH (50 mL) was degassed by a stream of argon gas for 15 min. The reaction flask was sealed and placed in a pre-heated oil bath (115° C.). After stirring overnight, the reaction was cooled and filtered. The filter cake was washed with DCM and the filtrate was concentrated in vacuo. The resulting residue was dissolved in EtOAc (150 mL). EtOAC was sequentially washed with water (20 mL), brine (20 mL), dried over Na2SO4 and evaporated. The crude product was purified by silica chromatography (0-50% EtOAC in hexanes gradient) to give 2,5-dimethyl-4-(pyridin-3-yl)aniline as a yellow solid; ESMS m/z 199.1 (M+H+). was degassed by a stream of argon gas for 15 min The reaction flask was sealed placed in a pre-heated oil bath (115° C.) the reaction was cooled filtered The filter cake was washed with DCM the filtrate was concentrated in vacuo The resulting residue was dissolved in EtOAc (150 mL) EtOAC was sequentially washed with water (20 mL), brine (20 mL) dried over Na2SO4 evaporated The crude product was purified by silica chromatography (0-50% EtOAC in hexanes gradient)

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

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