2-bromo-5-chloroaniline

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:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2-bromo-5-chloroaniline (20.0 g, 96.9 mmol) in 1,4-dioxane (200 ml) were added triethylamine (54.0 ml, 487 mmol) and [1,1-bis(diphenylphosphino)ferrocene]dichloropalladium(II) dichloromethane complex (3.96 g, 4.84 mmol), and under a nitrogen stream, 4,4,5,5-tetramethyl-1,3,2-dioxaborolane (42.3 ml, 290 mmol) was added dropwise. The mixture was stirred at 100° C. for 10.5 hr. The mixture was allowed to cool to room temperature and filtered through celite. To the filtrate was added dropwise methanol (25 ml) at 0° C. The solvent was evaporated under reduced pressure, and the obtained residue was purified by silica gel chromatography (hexane:ethyl acetate=20:1) to give 5-chloro-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenylamine (16.5 g, yield. 65%). to cool to room temperature filtered through celite To the filtrate was added dropwise methanol (25 ml) at 0° C The solvent was evaporated under reduced pressure the obtained residue was purified by silica gel chromatography (hexane:ethyl acetate=20:1)

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2-bromo-5-chloroaniline (20.0 g, 96.9 mmol) in 1,4-dioxane (200 ml) were added triethylamine (54.0 ml, 487 mmol) and [1,1-bis(diphenylphosphino)ferrocene]dichloropalladium(II) dichloromethane complex (3.96 g, 4.84 mmol), and under a nitrogen stream, 4,4,5,5-tetramethyl-1,3,2-dioxaborolane (42.3 ml, 290 mmol) was added dropwise. The mixture was stirred at 100° C. for 10.5 hr. The mixture was allowed to cool to room temperature and filtered through celite. To the filtrate was added dropwise methanol (25 ml) at 0° C. The solvent was evaporated under reduced pressure, and the obtained residue was purified by silica gel chromatography (hexane:ethyl acetate=20:1) to give 5-chloro-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenylamine (16.5 g, yield. 65%). to cool to room temperature filtered through celite To the filtrate was added dropwise methanol (25 ml) at 0° C The solvent was evaporated under reduced pressure the obtained residue was purified by silica gel chromatography (hexane:ethyl acetate=20:1)

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-Bromo-5-chloroaniline (CAS#823-57-4; 5 g), 4-fluorophenylboronic acid (3.56 g) and cesium carbonate (31.6 g) were combined in THF (70 ml) and water (35 ml). The mixture was degassed by bubbling argon through the solution. After addition of [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (886 mg) the reaction mixture was stirred 1 h at 80° C. in a sealed tube. The reaction mixture was diluted with EtOAc, washed with water, dried over Na2SO4, evaporated and purified by chromatography (silica gel, 0% to 30% EtOAc in heptane). The product was finally bulb-to-bulb distilled at 0.3 mbar and 120-130° C. oven temperature to give the title compound (5.07 g) as a light yellow liquid. The mixture was degassed by bubbling argon through the solution After addition of [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (886 mg) the reaction mixture The reaction mixture was diluted with EtOAc washed with water dried over Na2SO4 evaporated purified by chromatography (silica gel, 0% to 30% EtOAc in heptane) distilled at 0.3 mbar and 120-130° C. oven temperature

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

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

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-Bromo-5-chloroaniline (85.2 g, 0.41 mol) was dissolved in 1 L of acetonitrile followed by the addition of dimethydisulfide (30.0 mL, 0.33 mol). The flask was immersed in a water bath warmed to 60° C., equipped with a reflux condenser, and tert-butyl nitrite (54.0, 0.45 mol) was added in portions over 15 minutes. Once the addition was complete, the reaction was refluxed for 2 hours. After cooling to room temperature, the acetonitrile was evaporated, followed by re-dissolving in dichloromethane and subsequent concentration to remove remaining acetonitrile. The residue was re-dissolved in a minimal amount of dichloromethane and diluted with hexanes until precipitation was initiated. The mixture was filtered through a plug of silica and washed with hexanes. The filtrate was then concentrated in vacuo and crystallized upon cooling. 1-Bromo-4-chloro-2-methylsulfanylbenzene (52.0 g, 53%) was isolated via suction filtration. The flask was immersed in a water bath equipped with a reflux condenser Once the addition the reaction was refluxed for 2 hours After cooling to room temperature the acetonitrile was evaporated by re-dissolving in dichloromethane subsequent concentration to remove The residue was re-dissolved in a minimal amount of dichloromethane diluted with hexanes until precipitation The mixture was filtered through a plug of silica washed with hexanes The filtrate was then concentrated in vacuo crystallized upon cooling

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

Procedure: 1-Bromo-4-chloro-2-nitrobenzene (140 g, 0.59 mol) was dissolved in 2.5 L of MeOH with gentle heating (50° C.) in a hot water bath. A solution of ammonium formate (303 g, 4.81 mol) in 500 mL of water was added. Zinc powder (155 g, 2.36 mol) was added in small portions, resulting in heat evolution and refluxing of the solvent. Subsequent additions were made cautiously as to avoid build up of excess unreacted zinc. The reaction was cooled to room temperature and filtered through a large plug of CELITE® filter aid. The filtrate was then concentrated until a biphasic mixture of red oil and water was evident. The product was extracted with five 200 mL portions of diethyl ether. The organics were combined and dried over sodium sulfate, decanted, and concentrated in vacuo to a reddish-brown oil. The oil was redissolved in 150 mL of dichloromethane/hexanes and filtered through a plug of silica gel. The filtrate was concentrated to an orange oil. Addition of hexanes (200 mL) and cooling in a dry ice bath resulted in precipitation of 2-bromo-5-chloroaniline as a pale yellow solid (92.1 g, 75%) that was collected via vacuum filtration. resulting in heat evolution refluxing of the solvent The reaction was cooled to room temperature filtered through a large plug of CELITE® filter aid The filtrate was then concentrated until a biphasic mixture of red oil and water The product was extracted with five 200 mL portions of diethyl ether dried over sodium sulfate decanted concentrated in vacuo to a reddish-brown oil The oil was redissolved in 150 mL of dichloromethane/hexanes filtered through a plug of silica gel The filtrate was concentrated to an orange oil Addition of hexanes (200 mL) cooling in a dry ice bath