2-bromo-4-iodo-1-methylbenzene

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

Procedure: A well stirred solution of 18.6 g (0.10 mol) of 3-bromo-p-toluidine in 80 mL of 6N HCl at 0° C. was treated with a solution of 7.35 g (0.11 mol) of sodium nitrite in 15 mL of water at a rate that maintained the temperature <10° C. The mixture was stirred for 45 minutes then cautiously treated with 33.2 g (0.20 mol) of potassium iodide at 0° C. The mixture was treated with 300 mL of ether and washed (3×) with saturated aqueous sodium bisulfite. The organic layer was separated, dried over magnesium sulfate, filtered and concentrated under vacuum. The residue was redissolved in 50 mL of hexane, filtered through 30 g of silica and concentrated under vacuum to afford 15.6 g (0.053 mol, 53%) of the product which was determined to be 65% pure by 1H NMR. 1H NMR (200 MHz,CDCl3): 2.33 (s,3H), 6.97 (d,8 Hz,1H), 7.51 (dd;2,8 Hz,1H), 7.86 (d,2 Hz,1H). maintained the temperature <10° C washed (3×) with saturated aqueous sodium bisulfite The organic layer was separated dried over magnesium sulfate filtered concentrated under vacuum The residue was redissolved in 50 mL of hexane filtered through 30 g of silica concentrated under vacuum

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

Procedure: To a vigorously stirred mixture of 3-bromo-4-methylaniline (40 g, 215 mmol), sulfuric acid (360 mL) and H2O (900 mL) at 0° C. was added dropwise a NaNO2 solution (16.6 g, 240 mmol in 80 mL of H2O). The mixture was stirred at 0° C. for 1 hour and a solution of potassium iodide (64 g, 387 mmol in 160 mL of H2O) was added. The reaction was stirred for 8 hours at r.t. The aqueous layer was extracted with Et2O and the combined organic layers were washed with a 10% aqueous solution of Na2S2O3, dried over Na2SO4 and concentrated. The residue was filtered through a silica gel pad eluted with 10% EtOAc/hexane and concentrated to give 60 g of the title compound as a reddish syrup used as such. The reaction was stirred for 8 hours at r.t The aqueous layer was extracted with Et2O the combined organic layers were washed with a 10% aqueous solution of Na2S2O3 dried over Na2SO4 concentrated The residue was filtered through a silica gel pad eluted with 10% EtOAc/hexane concentrated

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

Procedure: To a vigorously stirred mixture of 3-bromo-4-methylaniline (40 g, 215 mmol), sulfuric acid (360 mL) and H2O (900 mL) at 0° C. was added dropwise a NaNO2 solution (16.6 g, 240 mmol in 80 mL of H2O). The mixture was stirred at 0° C. for 1 hour and a solution of potassium iodide (64 g, 387 mmol in 160 mL of H2O) was added. The reaction was stirred for 8 hours at r.t. The aqueous layer was extracted with Et2O and the combined organic layers were washed with a 10% aqueous solution of Na2S2O3, dried over Na2SO4 and concentrated. The residue was filtered through a silica gel pad eluted with 10% EtOAc/hexane and concentrated to give 60 g of the title compound as a reddish syrup used as such. The reaction was stirred for 8 hours at r.t The aqueous layer was extracted with Et2O the combined organic layers were washed with a 10% aqueous solution of Na2S2O3 dried over Na2SO4 concentrated The residue was filtered through a silica gel pad eluted with 10% EtOAc/hexane concentrated

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

Procedure: A well stirred solution of 18.6 g (0.10 mol) of 3-bromo-p-toluidine in 80 mL of 6N HCl at 0° C. was treated with a solution of 7.35 g (0.11 mol) of sodium nitrite in 15 mL of water at a rate that maintained the temperature <10° C. The mixture was stirred for 45 minutes then cautiously treated with 33.2 g (0.20 mol) of potassium iodide at 0° C. The mixture was treated with 300 mL of ether and washed (3×) with saturated aqueous sodium bisulfite. The organic layer was separated, dried over magnesium sulfate, filtered and concentrated under vacuum. The residue was redissolved in 50 mL of hexane, filtered through 30 g of silica and concentrated under vacuum to afford 15.6 g (0.053 mol,53%) of the product which was determined to be 65% pure by 1H NMR. 1H NMR (200 MHz,CDCl3): 2.33 (s,3H), 6.97 (d,8 Hz,1H), 7.51 (dd;2,8 Hz,1H), 7.86 (d,2 Hz,1H). maintained the temperature <10° C washed (3×) with saturated aqueous sodium bisulfite The organic layer was separated dried over magnesium sulfate filtered concentrated under vacuum The residue was redissolved in 50 mL of hexane filtered through 30 g of silica concentrated under vacuum

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

Procedure: A well stirred solution of 18.6 g (0.10 mol) of 3-bromo-p-toluidine in 80 mL of 6N HCl at 0° C. was treated with a solution of 7.35 g (0.11 mol) of sodium nitrite in 15 mL of water at a rate that maintained the temperature <10° C. The mixture was stirred for 45 minutes then cautiously treated with 33.2 g (0.20 mol) of potassium iodide at 0° C. The mixture was treated with 300 mL of ether and washed (3×) with saturated aqueous sodium bisulfite. The organic layer was separated, dried over magnesium sulfate, filtered and concentrated under vacuum. The residue was redissolved in 50 mL of hexane, filtered through 30 g of silica and concentrated under vacuum to afford 15.6 g (0.053 mol, 53%) of the product which was determined to be 65% pure by 1H NMR. 1H NMR (200 MHz,CDCl3): 2.33 (s,3H), 6.97 (d,8 Hz,1H), 7.51 (dd;2,8 Hz,1H), 7.86 (d,2 Hz,1H). maintained the temperature <10° C washed (3×) with saturated aqueous sodium bisulfite The organic layer was separated dried over magnesium sulfate filtered concentrated under vacuum The residue was redissolved in 50 mL of hexane filtered through 30 g of silica concentrated under vacuum

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

Procedure: To a vigorously stirred mixture of 3-bromo-4-methylaniline (40 g, 215 mmol), sulfuric acid (360 mL) and H2O (900 mL) at 0° C. was added dropwise a NaNO2 solution (16.6 g, 240 mmol in 80 mL of H2O). The mixture was stirred at 0° C. for 1 hour and a solution of potassium iodide (64 g, 387 mmol in 160 mL of H2O) was added. The reaction was stirred for 8 hours at r.t. The aqueous layer was extracted with Et2O and the combined organic layers were washed with a 10% aqueous solution of Na2S2O3, dried over Na2SO4 and concentrated. The residue was filtered through a silica gel pad eluted with 10% EtOAc/hexane and concentrated to give 60 g of the title compound as a reddish syrup used as such. The reaction was stirred for 8 hours at r.t The aqueous layer was extracted with Et2O the combined organic layers were washed with a 10% aqueous solution of Na2S2O3 dried over Na2SO4 concentrated The residue was filtered through a silica gel pad eluted with 10% EtOAc/hexane concentrated