4-bromo-5-fluoro-2-methylaniline

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

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

Procedure: 2-Amino-3-(5-bromo-4-fluoro-7-methyl-2H-benzotriazol-2-yl)-2-methylpropionitrile [1.3 g, Rf=0.2 (1:1 EA/heptane)] was prepared using a procedure similar to that described in Example 1, part a and b, except starting from 5-bromo-4-fluoro-7-methyl-1H-benzotriazole. 5-Bromo-4-fluoro-7-methyl-1H-benzotriazole (4 g, 85%) was prepared using a procedure similar to that described in Example 11, part a, except starting from 4-bromo-3-fluoro-6-methyl-2-nitroaniline. 4-Bromo-3-fluoro-6-methyl-2-nitroaniline (6.1 g) was prepared using a procedure similar to that described in Example 39, part a, b and c, except starting from 4-bromo-5-fluoro-2-methylaniline (10 g).

Conditions: temp:75.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 4-Bromo-5-fluoro-2-methylaniline (5 g, 24.5 mmol) was dissolved in 1,2-dimethyldisulfane (35 mL, 394 mmol) and heated to 75° C. under nitrogen. Isoamyl nitrite (8.52 mL, 63.7 mmol) was added dropwise to the reaction via an addition funnel through a reflux condenser (˜1 drop/sec). (NOTE—a large exotherm may occur if addition is too fast.) After addition was complete, the reaction was heated to 95° C. for 1 hour and allowed to cool to ambient temperature. The reaction was concentrated and purified over silica gel (100% hexanes) to afford (4-bromo-5-fluoro-2-methylphenyl)(methyl)sulfane (4.9 g, 20.8 mmol, 85.0% yield) as an orange solid. (NOTE—a large exotherm may occur if addition ) After addition the reaction was heated to 95° C. for 1 hour to cool to ambient temperature The reaction was concentrated purified over silica gel (100% hexanes)

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: 2-Amino-3-(5-bromo-4-fluoro-7-methyl-2H-benzotriazol-2-yl)-2-methylpropionitrile [1.3 g, Rf=0.2 (1:1 EA/heptane)] was prepared using a procedure similar to that described in Example 1, part a and b, except starting from 5-bromo-4-fluoro-7-methyl-1H-benzotriazole. 5-Bromo-4-fluoro-7-methyl-1H-benzotriazole (4 g, 85%) was prepared using a procedure similar to that described in Example 11, part a, except starting from 4-bromo-3-fluoro-6-methyl-2-nitroaniline. 4-Bromo-3-fluoro-6-methyl-2-nitroaniline (6.1 g) was prepared using a procedure similar to that described in Example 39, part a, b and c, except starting from 4-bromo-5-fluoro-2-methylaniline (10 g).

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

Procedure: 2-Amino-3-(5-bromo-4-fluoro-7-methyl-2H-benzotriazol-2-yl)-2-methylpropionitrile [1.3 g, Rf=0.2 (1:1 EA/heptane)] was prepared using a procedure similar to that described in Example 1, part a and b, except starting from 5-bromo-4-fluoro-7-methyl-1H-benzotriazole. 5-Bromo-4-fluoro-7-methyl-1H-benzotriazole (4 g, 85%) was prepared using a procedure similar to that described in Example 11, part a, except starting from 4-bromo-3-fluoro-6-methyl-2-nitroaniline. 4-Bromo-3-fluoro-6-methyl-2-nitroaniline (6.1 g) was prepared using a procedure similar to that described in Example 39, part a, b and c, except starting from 4-bromo-5-fluoro-2-methylaniline (10 g).

Conditions: temp:75.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 4-Bromo-5-fluoro-2-methylaniline (5 g, 24.5 mmol) was dissolved in 1,2-dimethyldisulfane (35 mL, 394 mmol) and heated to 75° C. under nitrogen. Isoamyl nitrite (8.52 mL, 63.7 mmol) was added dropwise to the reaction via an addition funnel through a reflux condenser (˜1 drop/sec). (NOTE—a large exotherm may occur if addition is too fast.) After addition was complete, the reaction was heated to 95° C. for 1 hour and allowed to cool to ambient temperature. The reaction was concentrated and purified over silica gel (100% hexanes) to afford (4-bromo-5-fluoro-2-methylphenyl)(methyl)sulfane (4.9 g, 20.8 mmol, 85.0% yield) as an orange solid. (NOTE—a large exotherm may occur if addition ) After addition the reaction was heated to 95° C. for 1 hour to cool to ambient temperature The reaction was concentrated purified over silica gel (100% hexanes)

Conditions: temp:75.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 4-Bromo-5-fluoro-2-methylaniline (5 g, 24.5 mmol) was dissolved in 1,2-dimethyldisulfane (35 mL, 394 mmol) and heated to 75° C. under nitrogen. Isoamyl nitrite (8.52 mL, 63.7 mmol) was added dropwise to the reaction via an addition funnel through a reflux condenser (˜1 drop/sec). (NOTE—a large exotherm may occur if addition is too fast.) After addition was complete, the reaction was heated to 95° C. for 1 hour and allowed to cool to ambient temperature. The reaction was concentrated and purified over silica gel (100% hexanes) to afford (4-bromo-5-fluoro-2-methylphenyl)(methyl)sulfane (4.9 g, 20.8 mmol, 85.0% yield) as an orange solid. (NOTE—a large exotherm may occur if addition ) After addition the reaction was heated to 95° C. for 1 hour to cool to ambient temperature The reaction was concentrated purified over silica gel (100% hexanes)

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

Procedure: 73.6 mL of acetic anhydride was added with 80.0 g of 4-bromo-5-fluoro-2-methylphenylamine at room temperature, and stirred at this temperature for 10 minutes. Excess acetic anhydride was distilled off under reduced pressure, and the precipitated crystals were washed with water, to afford 77.6 g of the title compound as colorless crystal. Excess acetic anhydride was distilled off under reduced pressure the precipitated crystals were washed with water

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

Procedure: To a solution of 49.0 g of 5-fluoro-o-toluidine in 600 mL of dichloromethane was added 69.7 g of N-bromosuccinimide at 0° C., and stirred at this temperature for an hour. Then sodium thiosulfate aqueous solution was added, and the reaction solution was evaporated and diluted with ethyl acetate. The organic layer was washed successively with water and saturated brine and dried over anhydrous magnesium sulfate. Then the solvent was evaporated, and the precipitated crystals were washed with diethyl ether:n-hexane=1:10, to afford 81.6 g of the title compound as colorless crystals. the reaction solution was evaporated diluted with ethyl acetate The organic layer was washed successively with water and saturated brine dried over anhydrous magnesium sulfate Then the solvent was evaporated the precipitated crystals were washed with diethyl ether

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

Procedure: 73.6 mL of acetic anhydride was added with 80.0 g of 4-bromo-5-fluoro-2-methylphenylamine at room temperature, and stirred at this temperature for 10 minutes. Excess acetic anhydride was distilled off under reduced pressure, and the precipitated crystals were washed with water, to afford 77.6 g of the title compound as colorless crystal. Excess acetic anhydride was distilled off under reduced pressure the precipitated crystals were washed with water