1-Bromo-4-chloro-5-fluoro-2-methylbenzene

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: 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)

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

Procedure: A solution of 75 mmol of 1-bromo-4-chloro-5-fluoro-2-methyl-benzene, 75 mmol of 1-bromo-pyrrolidine-2,5-dione and 0.74 mmol of benzoyl peroxide in 100 ml of carbon tetrachloride is heated to reflux for 15 hours. After evaporation of the solvent, the residue is partitioned between water and ethyl acetate. The organic layer is washed with water, and then with brine, 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. to reflux for 15 hours After evaporation of the solvent the residue is partitioned between water and ethyl acetate The organic layer is washed with water with brine, dried over sodium sulfate filtered concentrated under reduced pressure The resulting residue is purified by flash chromatography (SiO2 60 F)