5-bromo-2-chloro-4-methylaniline

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

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

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

Procedure: In an autoclave, a mixture of 253 mmol of 1-bromo-4-chloro-2-methyl-5-nitro-benzene [10289-13-1], 2 g of Raney nickel (60% aqueous) and 1.5 g of formamidine acetate in 102 ml of methanol is stirred under an atmosphere of hydrogen (pressure 12 bars) at 80° C. for 1 hour. The mixture is cooled to room temperature, filtered and evaporated. The residue is partitioned between aqueous saturated sodium bicarbonate-solution and tert-butyl-methyl ether. The aqueous phase is extracted with tert-butyl-methyl ether. The combined organic phases are dried over sodium sulfate, filtered and concentrated under reduced pressure. The resulting residue is purified by flash chromatography (SiO2 60 F) to afford the title compound which is identified based on the Rf value. The mixture is cooled to room temperature filtered evaporated The residue is partitioned between aqueous saturated sodium bicarbonate-solution and tert-butyl-methyl ether The aqueous phase is extracted with tert-butyl-methyl ether The combined organic phases are dried over sodium sulfate filtered concentrated under reduced pressure The resulting residue is purified by flash chromatography (SiO2 60 F)

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

Procedure: 1.25 mol of 5-bromo-2-chloro-4-methyl-phenylamine are added to 750 ml of concentrated aqueous HCl and the mixture is stirred at 80° C. until formation of a homogenous suspension, then the mixture is cooled to 0° C. and a solution of 1.38 mmol of sodium nitrite in 330 ml of water is added dropwise over 1 hour. The mixture is stirred for an additional 20 minutes and then a solution of 700 ml of fluoroboric acid (prepared by dissolving 264 g of boric acid in 744 ml of 40% aqueous hydrofluoric acid) is added. After 30 minutes of stirring, the separated fluoroborate is filtered off, washed successively with small amounts of fluoroboric acid solution, ethanol and water, and dried in vacuo. Thermal decomposition of the fluoroborate is carried out in a flask at 130-170° C. The distillate is partitioned between water and diethyl ether. The organic phase is washed successively with 10% aqueous NaOH, 3N aqueous HCl and water, dried over sodium sulfate, filtered and concentrated under reduced pressure. The resulting residue is purified by flash chromatography (SiO2 60 F) to afford the title compound which is identified based on the Rf value. the mixture is cooled to 0° C. The mixture is stirred for an additional 20 minutes After 30 minutes of stirring the separated fluoroborate is filtered off washed successively with small amounts of fluoroboric acid solution, ethanol and water dried in vacuo Thermal decomposition of the fluoroborate is carried out in a flask at 130-170° C The distillate is partitioned between water and diethyl ether The organic phase is washed successively with 10% aqueous NaOH, 3N aqueous HCl and water dried over sodium sulfate filtered concentrated under reduced pressure The resulting residue is purified by flash chromatography (SiO2 60 F)