4-fluoro-2-methylaniline

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:

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: Bromine (0.5 mole) is added over 1 hour to stirred 4-fluoro-2-toluidine (0.5 mole) at 100° C. illuminated with a high wattage lamp. The crude benzyl bromide is used as prepared. illuminated with a high wattage lamp as prepared

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

Procedure: 5-Fluoro-2-nitrotoluene (0.5 mole) in ethyl acetate (600 ml.) is hydrogenated at 40 p.s.i. of hydrogen over Pd/C catalyst (1%, 2 teaspoons) at room temperature until the theoretical amount of hydrogen has been taken up. The catalyst is filtered off, and the solvent evaporated to give the crude oil of 4-fluoro-2-toluidine. at room temperature The catalyst is filtered off the solvent evaporated

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

Procedure: A solution of 4-fluoro-2-methylaniline (about 1 g) in chloroform (5 ml) was added dropwise to a solution of ethyl 3-ethoxy-2-(2',5'-difluoro-3'-methyl-4'-nitrobenzoyl)acrylate (2.0 g) in chloroform (10 ml) at room temperature (while confirming the disappearance of the acrylate by tlc). After the mixture was stirred for 10 minutes, the solvent and the like were distilled off. Potassium carbonate (800 mg) was added to a solution of the whole amount of the residue in dimethylformamide (3 ml), and the mixture was stirred at 110° C. for 20 minutes. Chloroform and water were added to the reaction mixture to collect an organic layer. After the organic layer was dried over anhydrous magnesium sulfate, the solvent was distilled off. Ethanol was added to the residue to disperse it therein, and filtration was conducted to obtain the title compound (1.1 g) as a pale yellow powder. the solvent and the like were distilled off Potassium carbonate (800 mg) was added to a solution of the whole amount of the residue in dimethylformamide (3 ml) the mixture was stirred at 110° C. for 20 minutes Chloroform and water were added to the reaction mixture to collect an organic layer After the organic layer was dried over anhydrous magnesium sulfate the solvent was distilled off Ethanol was added to the residue to disperse it filtration

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Stirred acetic anhydride, 300 mL, was cooled to about 70° C., and 25.1 grams (0.20 mole) of 4-fluoro-2-methylaniline was added dropwise during a 30 minute period. Upon completion of addition, the reaction mixture was stirred at about 10° C. for an additional 15 minutes. In a separate reaction vessel, acetyl nitrate was prepared by the dropwise addition of 14.9 mL of 90% nitric acid to 30 mL of stirred, cold (0°-15° C.) acetic anhydride during a 15 minute period. The so-prepared acetyl nitrate was cooled to about -5° C., placed in a dropping funnel, and added dropwise during a 30 minute period to the 2-methylaniline solution. Upon completion of addition, the reaction mixture was stirred an additional 5 hours. After this time the reaction mixture was poured into 400 grams of ice. The resultant solid was collected by filtration, washed with water, and dried at 60° C. under vacuum, yielding 23.0 grams of 5-fluoro-2-methylcarbonylamino-3-methylnitrobenzene, mp 167°-172° C. The NMR spectrum was consistent with the proposed structure. Upon completion of addition of stirred placed in a dropping funnel Upon completion of addition the reaction mixture was stirred an additional 5 hours The resultant solid was collected by filtration washed with water dried at 60° C. under vacuum