1,3-dibromo-2-chloro-5-methylbenzene

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

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

Procedure: To 1,3-dibromo-2-chloro-5-methylbenzene (1000 mg, 3.52 mmol) was added NBS (688 mg, 3.87 mmol) and AIBN (57.7 mg, 0.352 mmol). The mixture was stirred at room temperature for 30 minutes and then heated to 80° C. overnight. The solution was evaporated and the residue was purified by silica gel chromatography (0-5% EtOAc/heaxnes) to provide the title compound (740 mg) as a clear oil. heated to 80° C. overnight The solution was evaporated the residue was purified by silica gel chromatography (0-5% EtOAc/heaxnes)

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

Procedure: To an Argon sparged solution of 1,3-dibromo-2-chloro-5-methylbenzene (5 g, 17.6 mmol), benzophenone imine (3.1 mL, 18.5 mmol), sodium tert-butoxide (2.53 g, 26.4 mmol) in toluene, (S)-BINAP (1.6 g, 2.6 mmol) and Pd2(dba)3 (0.81 g, 0.88 mmol) were added and the reaction was heated in an oil bath. When the temperature reached 60° C. an exotherm was noted, with reflux of the solvent. Heating was maintained and the reaction was complete after 1.5 hours. The reaction mixture was cooled, diluted with Et2O and stirred with Siliabond DMT (Pd scavenger), and was then filtered through Celite. The filtrate was washed with water, brine, dried (MgSO4), and concentrated to afford a sticky brown residue. The residue was dissolved in THF (60 mL) and aqueous 6.0 M HCl solution was added. The reaction mixture was stirred for 30 minutes, partitioned with Et2O and 1M NaOH was added until the aqueous layer was pH 9. The layers were separated and the organic layer was washed with water, brine, dried (MgSO4), and concentrated. Purification by flash chromatography (SiO2, 0-20% EtOAc in heptane) furnished 3-bromo-2-chloro-5-methylaniline (1.7 g) with a small amount of benzophenone as a contaminant: 1H NMR (300 MHz, CDCl3) δ 2.21 (s, 3H) 4.11 (br s, 2H) 6.52 (s, 1H) 6.85 (s, 1H). the reaction was heated in an oil bath reached 60° C. with reflux of the solvent Heating was maintained The reaction mixture was cooled was then filtered through Celite The filtrate was washed with water, brine dried (MgSO4) concentrated to afford a sticky brown residue partitioned with Et2O and 1M NaOH was added until the aqueous layer The layers were separated the organic layer was washed with water, brine dried (MgSO4) concentrated Purification by flash chromatography (SiO2, 0-20% EtOAc in heptane)

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

Procedure: To an Argon sparged solution of 1,3-dibromo-2-chloro-5-methylbenzene (5 g, 17.6 mmol), benzophenone imine (3.1 mL, 18.5 mmol), sodium tert-butoxide (2.53 g, 26.4 mmol) in toluene, (S)-BINAP (1.6 g, 2.6 mmol) and Pd2(dba)3 (0.81 g, 0.88 mmol) were added and the reaction was heated in an oil bath. When the temperature reached 60° C. an exotherm was noted, with reflux of the solvent. Heating was maintained and the reaction was complete after 1.5 hours. The reaction mixture was cooled, diluted with Et2O and stirred with Siliabond DMT (Pd scavenger), and was then filtered through Celite. The filtrate was washed with water, brine, dried (MgSO4), and concentrated to afford a sticky brown residue. The residue was dissolved in THF (60 mL) and aqueous 6.0 M HCl solution was added. The reaction mixture was stirred for 30 minutes, partitioned with Et2O and 1M NaOH was added until the aqueous layer was pH 9. The layers were separated and the organic layer was washed with water, brine, dried (MgSO4), and concentrated. Purification by flash chromatography (SiO2, 0-20% EtOAc in heptane) furnished 3-bromo-2-chloro-5-methylaniline (1.7 g) with a small amount of benzophenone as a contaminant: 1H NMR (300 MHz, CDCl3) δ 2.21 (s, 3H) 4.11 (br s, 2H) 6.52 (s, 1H) 6.85 (s, 1H). the reaction was heated in an oil bath reached 60° C. with reflux of the solvent Heating was maintained The reaction mixture was cooled was then filtered through Celite The filtrate was washed with water, brine dried (MgSO4) concentrated to afford a sticky brown residue partitioned with Et2O and 1M NaOH was added until the aqueous layer The layers were separated the organic layer was washed with water, brine dried (MgSO4) concentrated Purification by flash chromatography (SiO2, 0-20% EtOAc in heptane)

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

Procedure: To an Argon sparged solution of 1,3-dibromo-2-chloro-5-methylbenzene (5 g, 17.6 mmol), benzophenone imine (3.1 mL, 18.5 mmol), sodium tert-butoxide (2.53 g, 26.4 mmol) in toluene, (S)-BINAP (1.6 g, 2.6 mmol) and Pd2(dba)3 (0.81 g, 0.88 mmol) were added and the reaction was heated in an oil bath. When the temperature reached 60° C. an exotherm was noted, with reflux of the solvent. Heating was maintained and the reaction was complete after 1.5 hours. The reaction mixture was cooled, diluted with Et2O and stirred with Siliabond DMT (Pd scavenger), and was then filtered through Celite. The filtrate was washed with water, brine, dried (MgSO4), and concentrated to afford a sticky brown residue. The residue was dissolved in THF (60 mL) and aqueous 6.0 M HCl solution was added. The reaction mixture was stirred for 30 minutes, partitioned with Et2O and 1M NaOH was added until the aqueous layer was pH 9. The layers were separated and the organic layer was washed with water, brine, dried (MgSO4), and concentrated. Purification by flash chromatography (SiO2, 0-20% EtOAc in heptane) furnished 3-bromo-2-chloro-5-methylaniline (1.7 g) with a small amount of benzophenone as a contaminant: 1H NMR (300 MHz, CDCl3) δ 2.21 (s, 3H) 4.11 (br s, 2H) 6.52 (s, 1H) 6.85 (s, 1H). the reaction was heated in an oil bath reached 60° C. with reflux of the solvent Heating was maintained The reaction mixture was cooled was then filtered through Celite The filtrate was washed with water, brine dried (MgSO4) concentrated to afford a sticky brown residue partitioned with Et2O and 1M NaOH was added until the aqueous layer The layers were separated the organic layer was washed with water, brine dried (MgSO4) concentrated Purification by flash chromatography (SiO2, 0-20% EtOAc in heptane)

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

Procedure: To an Argon sparged solution of 1,3-dibromo-2-chloro-5-methylbenzene (5 g, 17.6 mmol), benzophenone imine (3.1 mL, 18.5 mmol), sodium tert-butoxide (2.53 g, 26.4 mmol) in toluene, (S)-BINAP (1.6 g, 2.6 mmol) and Pd2(dba)3 (0.81 g, 0.88 mmol) were added and the reaction was heated in an oil bath. When the temperature reached 60° C. an exotherm was noted, with reflux of the solvent. Heating was maintained and the reaction was complete after 1.5 hours. The reaction mixture was cooled, diluted with Et2O and stirred with Siliabond DMT (Pd scavenger), and was then filtered through Celite. The filtrate was washed with water, brine, dried (MgSO4), and concentrated to afford a sticky brown residue. The residue was dissolved in THF (60 mL) and aqueous 6.0 M HCl solution was added. The reaction mixture was stirred for 30 minutes, partitioned with Et2O and 1M NaOH was added until the aqueous layer was pH 9. The layers were separated and the organic layer was washed with water, brine, dried (MgSO4), and concentrated. Purification by flash chromatography (SiO2, 0-20% EtOAc in heptane) furnished 3-bromo-2-chloro-5-methylaniline (1.7 g) with a small amount of benzophenone as a contaminant: 1H NMR (300 MHz, CDCl3) δ 2.21 (s, 3H) 4.11 (br s, 2H) 6.52 (s, 1H) 6.85 (s, 1H). the reaction was heated in an oil bath reached 60° C. with reflux of the solvent Heating was maintained The reaction mixture was cooled was then filtered through Celite The filtrate was washed with water, brine dried (MgSO4) concentrated to afford a sticky brown residue partitioned with Et2O and 1M NaOH was added until the aqueous layer The layers were separated the organic layer was washed with water, brine dried (MgSO4) concentrated Purification by flash chromatography (SiO2, 0-20% EtOAc in heptane)

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

Procedure: To 1,3-dibromo-2-chloro-5-methylbenzene (1000 mg, 3.52 mmol) was added NBS (688 mg, 3.87 mmol) and AIBN (57.7 mg, 0.352 mmol). The mixture was stirred at room temperature for 30 minutes and then heated to 80° C. overnight. The solution was evaporated and the residue was purified by silica gel chromatography (0-5% EtOAc/heaxnes) to provide the title compound (740 mg) as a clear oil. heated to 80° C. overnight The solution was evaporated the residue was purified by silica gel chromatography (0-5% EtOAc/heaxnes)

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

Procedure: To 1,3-dibromo-2-chloro-5-methylbenzene (1000 mg, 3.52 mmol) was added NBS (688 mg, 3.87 mmol) and AIBN (57.7 mg, 0.352 mmol). The mixture was stirred at room temperature for 30 minutes and then heated to 80° C. overnight. The solution was evaporated and the residue was purified by silica gel chromatography (0-5% EtOAc/heaxnes) to provide the title compound (740 mg) as a clear oil. heated to 80° C. overnight The solution was evaporated the residue was purified by silica gel chromatography (0-5% EtOAc/heaxnes)

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

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

Procedure: To an Argon sparged solution of 1,3-dibromo-2-chloro-5-methylbenzene (5 g, 17.6 mmol), benzophenone imine (3.1 mL, 18.5 mmol), sodium tert-butoxide (2.53 g, 26.4 mmol) in toluene, (S)-BINAP (1.6 g, 2.6 mmol) and Pd2(dba)3 (0.81 g, 0.88 mmol) were added and the reaction was heated in an oil bath. When the temperature reached 60° C. an exotherm was noted, with reflux of the solvent. Heating was maintained and the reaction was complete after 1.5 hours. The reaction mixture was cooled, diluted with Et2O and stirred with Siliabond DMT (Pd scavenger), and was then filtered through Celite. The filtrate was washed with water, brine, dried (MgSO4), and concentrated to afford a sticky brown residue. The residue was dissolved in THF (60 mL) and aqueous 6.0 M HCl solution was added. The reaction mixture was stirred for 30 minutes, partitioned with Et2O and 1M NaOH was added until the aqueous layer was pH 9. The layers were separated and the organic layer was washed with water, brine, dried (MgSO4), and concentrated. Purification by flash chromatography (SiO2, 0-20% EtOAc in heptane) furnished 3-bromo-2-chloro-5-methylaniline (1.7 g) with a small amount of benzophenone as a contaminant: 1H NMR (300 MHz, CDCl3) δ 2.21 (s, 3H) 4.11 (br s, 2H) 6.52 (s, 1H) 6.85 (s, 1H). the reaction was heated in an oil bath reached 60° C. with reflux of the solvent Heating was maintained The reaction mixture was cooled was then filtered through Celite The filtrate was washed with water, brine dried (MgSO4) concentrated to afford a sticky brown residue partitioned with Et2O and 1M NaOH was added until the aqueous layer The layers were separated the organic layer was washed with water, brine dried (MgSO4) concentrated Purification by flash chromatography (SiO2, 0-20% EtOAc in heptane)

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

Procedure: To an Argon sparged solution of 1,3-dibromo-2-chloro-5-methylbenzene (5 g, 17.6 mmol), benzophenone imine (3.1 mL, 18.5 mmol), sodium tert-butoxide (2.53 g, 26.4 mmol) in toluene, (S)-BINAP (1.6 g, 2.6 mmol) and Pd2(dba)3 (0.81 g, 0.88 mmol) were added and the reaction was heated in an oil bath. When the temperature reached 60° C. an exotherm was noted, with reflux of the solvent. Heating was maintained and the reaction was complete after 1.5 hours. The reaction mixture was cooled, diluted with Et2O and stirred with Siliabond DMT (Pd scavenger), and was then filtered through Celite. The filtrate was washed with water, brine, dried (MgSO4), and concentrated to afford a sticky brown residue. The residue was dissolved in THF (60 mL) and aqueous 6.0 M HCl solution was added. The reaction mixture was stirred for 30 minutes, partitioned with Et2O and 1M NaOH was added until the aqueous layer was pH 9. The layers were separated and the organic layer was washed with water, brine, dried (MgSO4), and concentrated. Purification by flash chromatography (SiO2, 0-20% EtOAc in heptane) furnished 3-bromo-2-chloro-5-methylaniline (1.7 g) with a small amount of benzophenone as a contaminant: 1H NMR (300 MHz, CDCl3) δ 2.21 (s, 3H) 4.11 (br s, 2H) 6.52 (s, 1H) 6.85 (s, 1H). the reaction was heated in an oil bath reached 60° C. with reflux of the solvent Heating was maintained The reaction mixture was cooled was then filtered through Celite The filtrate was washed with water, brine dried (MgSO4) concentrated to afford a sticky brown residue partitioned with Et2O and 1M NaOH was added until the aqueous layer The layers were separated the organic layer was washed with water, brine dried (MgSO4) concentrated Purification by flash chromatography (SiO2, 0-20% EtOAc in heptane)

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

Procedure: To an Argon sparged solution of 1,3-dibromo-2-chloro-5-methylbenzene (5 g, 17.6 mmol), benzophenone imine (3.1 mL, 18.5 mmol), sodium tert-butoxide (2.53 g, 26.4 mmol) in toluene, (S)-BINAP (1.6 g, 2.6 mmol) and Pd2(dba)3 (0.81 g, 0.88 mmol) were added and the reaction was heated in an oil bath. When the temperature reached 60° C. an exotherm was noted, with reflux of the solvent. Heating was maintained and the reaction was complete after 1.5 hours. The reaction mixture was cooled, diluted with Et2O and stirred with Siliabond DMT (Pd scavenger), and was then filtered through Celite. The filtrate was washed with water, brine, dried (MgSO4), and concentrated to afford a sticky brown residue. The residue was dissolved in THF (60 mL) and aqueous 6.0 M HCl solution was added. The reaction mixture was stirred for 30 minutes, partitioned with Et2O and 1M NaOH was added until the aqueous layer was pH 9. The layers were separated and the organic layer was washed with water, brine, dried (MgSO4), and concentrated. Purification by flash chromatography (SiO2, 0-20% EtOAc in heptane) furnished 3-bromo-2-chloro-5-methylaniline (1.7 g) with a small amount of benzophenone as a contaminant: 1H NMR (300 MHz, CDCl3) δ 2.21 (s, 3H) 4.11 (br s, 2H) 6.52 (s, 1H) 6.85 (s, 1H). the reaction was heated in an oil bath reached 60° C. with reflux of the solvent Heating was maintained The reaction mixture was cooled was then filtered through Celite The filtrate was washed with water, brine dried (MgSO4) concentrated to afford a sticky brown residue partitioned with Et2O and 1M NaOH was added until the aqueous layer The layers were separated the organic layer was washed with water, brine dried (MgSO4) concentrated Purification by flash chromatography (SiO2, 0-20% EtOAc in heptane)