4-bromo-2-chloro-6-methylaniline

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Step G1. To an ice-water-cooled and stirred solution of 2-amino-5-bromo-3-chlorotoluene (12 g, 54 mmol) in a mixture of 100 mL of acetic acid, 43 mL of H2O and 11.5 mL of concentrated HCl was added dropwise a solution of NaNO2 (4.48 g, 65 mmol) in 15 mL of H2O. The reaction mixture was stirred for 30 min and was then added to an 112 mL solution of 50% H3PO2 cooled at 0° C. After being stirred for 6 h at 0° C., the reaction mixture was allowed to stand at room temperature overnight. The solid was filtered and washed with water, then dried in vacuum. 3-Chloro-5-bromo-toluene (9 g, 81%) was obtained as brown solid. Crystals. 1H NMR (CDCl3): δ 2.31 (s, 3H), 7.10 (s, 1H), 7.21 (s, 1H), 7.31 (s, 1H). After being stirred for 6 h at 0° C. to stand at room temperature overnight The solid was filtered washed with water dried in vacuum

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Step G1. To an ice-water-cooled and stirred solution of 2-amino-5-bromo-3-chlorotoluene (12 g, 54 mmol) in a mixture of 100 mL of acetic acid, 43 mL of H2O and 11.5 mL of concentrated HCl was added dropwise a solution of NaNO2 (4.48 g, 65 mmol) in 15 mL of H2O. The reaction mixture was stirred for 30 min and was then added to an 112 mL solution of 50% H3PO2 cooled at 0° C. After being stirred for 6 h at 0° C., the reaction mixture was allowed to stand at room temperature overnight. The solid was filtered and washed with water, then dried in vacuum. 3-Chloro-5-bromo-toluene (9 g, 81%) was obtained as brown solid. Crystals. 1H NMR (CDCl3): δ 2.31 (s, 3H), 7.10 (s, 1H), 7.21 (s, 1H), 7.31 (s, 1H). After being stirred for 6 h at 0° C. to stand at room temperature overnight The solid was filtered washed with water dried in vacuum

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

Procedure: 3,3-dimethylbutanoyl chloride (3.37 g, 3.5 mL, 25 mmol) and triethylamine (2.53 g, 3.5 mL, 25 mmol) were added to a solution of 4-Bromo-2-chloro-6-methyl-phenylamine (5.0 g, 25 mmol) in acetonitrile (30 mL). The reaction mixture was stirred at room temperature for 4 hours. Water was added to the mixture and the precipitate formed collected to give the title compound as a powder (7.46 g, 100% yield). the precipitate formed collected

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

Procedure: 3,3-Dimethylbutanoyl chloride (3.37 g, 3.5 mL, 25 mmol) and triethylamine (2.53 g, 3.5 mL, 25 mmol) were added to a solution. of 4-Bromo-2-chloro-6-methylphenylamine (5.0 g, 25 mmol) in acetonitrile (30 mL). The reaction mixture was stirred at room temperature for 4 hours. Water was added to the mixture and the precipitate formed collected to give the title compound as a powder (7.46 g, 100% yield). the precipitate formed collected

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

Procedure: 3,3-Dimethylbutanoyl chloride (3.37 g, 3.5 mL, 25 mmol) and triethylamine (2.53 g, 3.5 mL, 25 mmol) were added to a solution. of 4-Bromo-2-chloro-6-methylphenylamine (5.0 g, 25 mmol) in acetonitrile (30 mL). The reaction mixture was stirred at room temperature for 4 hours. Water was added to the mixture and the precipitate formed collected to give the title compound as a powder (7.46 g, 100% yield). the precipitate formed collected

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

Procedure: 3,3-Dimethylbutanoyl chloride (3.37 g, 3.5 mL, 25 mmol) and triethylamine (2.53 g, 3.5 mL, 25 mmol) were added to a solution of 4-Bromo-2-chloro-6-methyl-phenylamine (5.0 g, 25 mmol) in acetonitrile (30 mL). The reaction mixture was stirred at room temperature for 4 hours. Water was added to the mixture and the precipitate formed collected to give the title compound as a powder (7.46 g, 100% yield). the precipitate formed collected

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

Procedure: 3,3-Dimethylbutanoyl chloride (3.37 g, 3.5 mL, 25 mmol) and triethylamine (2.53 g, 3.5 mL, 25 mmol) were added to a solution of 4-Bromo-2-chloro-6-methylphenylamine (5.0 g, 25 mmol) in acetonitrile (30 mL). The reaction mixture was stirred at room temperature for 4 hours. Water was added to the mixture and the precipitate formed collected to give the title compound as a powder (7.46 g, 100% yield). the precipitate formed collected

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

Procedure: 3,3-Dimethylbutanoyl chloride (3.37 g, 3.5 mL, 25 mmol) and triethylamine (2.53 g, 3.5 mL, 25 mmol) were added to a solution of 4-bromo-2-chloro-6-methyl-phenylamine (5.0 g, 25 mmol) in acetonitrile (30 mL). The reaction mixture was stirred at room temperature for 4 hours. Water was added to the mixture, and the precipitate that formed was collected to give the title compound as a powder (7.46 g, 100% yield). the precipitate that formed was collected

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

Procedure: Under protective nitrogen gas 2.02 g (9.0 mmol) palladium(II)acetate and 2.82 g (9.0 mmol) tri-o-tolylphosphine were added to a mixture of 25.0 g (113 mmol) 4-bromo-2-chloro-6-methyl-aniline, 19.9 g (136 mmol) methyl 2-acetamidoacrylate, 350 ml triethylamine and 150 ml acetonitrile at ambient temperature. The reaction mixture was stirred for 18 hours at 80° C., evaporated down under reduced pressure, the residue was combined with 600 ml dichloromethane and water and filtered off from the insoluble precipitate. The organic phase was dried over sodium sulphate, evaporated down under reduced pressure and then combined with 200 ml of ethyl acetate/cyclohexane (3/1). The insoluble fraction was suction filtered and the mother liquor was purified by column chromatography through silica gel. The corresponding fractions were evaporated down under reduced pressure and combined with the insolublen fraction suction filtered previously. evaporated down under reduced pressure filtered off from the insoluble precipitate The organic phase was dried over sodium sulphate evaporated down under reduced pressure filtered the mother liquor was purified by column chromatography through silica gel The corresponding fractions were evaporated down under reduced pressure filtered previously

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

Procedure: 3,3-dimethylbutanoyl chloride (3.37 g, 3.5 mL, 25 mmol) and triethylamine (2.53 g, 3.5 mL, 25 mmol) were added to a solution of 4-Bromo-2-chloro-6-methyl-phenylamine (5.0 g, 25 mmol) in acetonitrile (30 mL). The reaction mixture was stirred at room temperature for 4 hours. Water was added to the mixture and the precipitate formed collected to give the title compound as a powder (7.46 g, 100% yield). the precipitate formed collected

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

Procedure: 3,3-Dimethylbutanoyl chloride (3.37 g, 3.5 mL, 25 mmol) and triethylamine (2.53 g, 3.5 mL, 25 mmol) were added to a solution of 4-Bromo-2-chloro-6-methyl-phenylamine (5.0 g, 25 mmol) in acetonitrile (30 mL). The reaction mixture was stirred at room temperature for 4 hours. Water was added to the mixture and the precipitate formed collected to give the title compound as a powder (7.46 g, 100% yield). the precipitate formed collected

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

Procedure: 3,3-Dimethylbutanoyl chloride (3.37 g, 3.5 mL, 25 mmol) and triethylamine (2.53 g, 3.5 mL, 25 mmol) were added to a solution of 4-Bromo-2-chloro-6-methyl-phenylamine (5.0 g, 25 mmol) in acetonitrile (30 mL). The reaction mixture was stirred at room temperature for 4 hours. Water was added to the mixture and the precipitate formed collected to give the title compound as a powder (7.46 g, 100% yield). the precipitate formed collected