N-(3,5-dimethylphenyl)acetamide

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

Procedure: A mixture of 3,5dimethylaniline (20 g, 165 mmol), acetic anhydride (24 mL, 247 mmol) and triethylamine (70 mL, 495 mmol) in methylene chloride (300 mL is stirred at room temperature for 16 hours. The mixture is washed with water, dried (magnesium sulfate) and rotary evaporated. The residue is triturated with hexane and filtered to afford N-acetyl-3,5-dimethylaniline (25 g). The mixture is washed with water dried (magnesium sulfate) and rotary evaporated The residue is triturated with hexane filtered

Conditions: temp:175.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 9.6 g (58.8 mmole) of N-acetyl-3,5-dimethylaniline, 8.13 g (58.8 mmole) of potassium carbonate (dried at 155° C. under vacuum), 23 g (147 mmole) of bromobenzene (dried over molecular sieves), and 1.12 g (5.9 mmole) of cuprous iodide was heated in a 175° C. oil bath under a reflux condenser under nitrogen for 18 hours. The mixture was cooled to room temperature and triturated with 1 liter of benzene. The solution was concentrated in vacuo. The residue was treated with 60 mL of EtOH and 7.76 g (118 mmole) of Potassium hydroxide and the resulting mixture was heated to reflux for two hours. The mixture was cooled and the solvent removed in vacuo. The residue was taken up in 150 mL of hexanes and 20 mL of EtOAc and the resulting solution was washed with 2×100 mL of 2N-aqueous HCl and 60 mL of water. The organic layer was dried over sodium sulfate, filtered and concentrated in vacuo. The residue was Purified by flash chromatography on 210 g of silica gel with 2 liters of 3:1 hexanes CH2Cl2 to give 5.5 g (47%) of a light red oil. The mixture was cooled to room temperature triturated with 1 liter of benzene The solution was concentrated in vacuo the resulting mixture was heated to reflux for two hours The mixture was cooled the solvent removed in vacuo 20 mL of EtOAc and the resulting solution was washed with 2×100 mL of 2N-aqueous HCl and 60 mL of water The organic layer was dried over sodium sulfate filtered concentrated in vacuo The residue was Purified by flash chromatography on 210 g of silica gel with 2 liters of 3:1 hexanes CH2Cl2

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

Procedure: To a solution of 15.2 g (125 mmole) of 3,5-dimethylaniline in 60 mL of toluene was added 15 g (146 mmole) of acetic anhydride, whereupon the internal temperature rose to 75° C. The mixture was allowed to cool to room temperature and the solvent was removed in vacuo. The residue was dissolved in 150 mL of hot ethyl acetate and the solution allowed to stand for 16 hours. The resulting mixture was cooled at 5° C. for 3 hours and the solid collected by filtration to give 18.43 g (90%) of off white crystals. rose to 75° C the solvent was removed in vacuo The residue was dissolved in 150 mL of hot ethyl acetate The resulting mixture was cooled at 5° C. for 3 hours the solid collected by filtration to give 18.43 g (90%) of off white crystals

Conditions: temp:175.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 9.6 g (58.8 mmole) of N-acetyl-3,5-dimethylaniline, 8.13 g (58.8 mmole) of potassium carbonate (dried at 155° C. under vacuum), 23 g (147 mmole) of bromobenzene (dried over molecular sieves), and 1.12 g (5.9 mmole) of cuprous iodide was heated in a 175° C. oil bath under a reflux condenser under nitrogen for 18 hours. The mixture was cooled to room temperature and triturated with 1 liter of benzene. The solution was concentrated in vacuo. The residue was treated with 60 mL of EtOH and 7.76 g (118 mmole) of potassium hydroxide and the resulting mixture was heated to reflux for two hours. The mixture was cooled and the solvent removed in vacuo. The residue was taken up in 150 mL of hexanes and 20 mL of EtOAc and the resulting solution was washed with 2×100 mL of 2N aqueous HCl and 60 mL of water. The organic layer was dried over sodium sulfate, filtered and concentrated in vacuo. The residue was purified by flash chromatography on 210 g of silica gel with 2 liters of 3:1 hexanes CH2Cl2 to give 5.5 g (47%) of a light red oil. The mixture was cooled to room temperature triturated with 1 liter of benzene The solution was concentrated in vacuo the resulting mixture was heated to reflux for two hours The mixture was cooled the solvent removed in vacuo 20 mL of EtOAc and the resulting solution was washed with 2×100 mL of 2N aqueous HCl and 60 mL of water The organic layer was dried over sodium sulfate filtered concentrated in vacuo The residue was purified by flash chromatography on 210 g of silica gel with 2 liters of 3:1 hexanes CH2Cl2

Conditions: temp:175.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 9.6 g (58.8 mmole) of N-acetyl-3,5-dimethylaniline, 8.13 g (58.8 mmole) of potassium carbonate (dried at 155° C. under vacuum), 23 g (147 mmole) of bromobenzene (dried over molecular sieves), and 1.12 g (5.9 mmole) of cuprous iodide was heated in a 175° C. oil bath under a reflux condenser under nitrogen for 18 hours. The mixture was cooled to room temperature and triturated with 1 liter of benzene. The solution was concentrated in vacuo. The residue was treated with 60 mL of EtOH and 7.76 g (118 mmole) of potassium hydroxide and the resulting mixture was heated to reflux for two hours. The mixture was cooled and the solvent removed in vacuo. The residue was taken up in 150 mL of hexanes and 20 mL of EtOAc and the resulting solution was washed with 2×100 mL of 2N aqueous HCl and 60 mL of water. The organic layer was dried over sodium sulfate, filtered and concentrated in vacuo. The residue was purified by flash chromatography on 210 g of silica gel with 2 liters of 3:1 hexanes CH2Cl2 to give 5.5 g (47%) of a light red oil. The mixture was cooled to room temperature triturated with 1 liter of benzene The solution was concentrated in vacuo the resulting mixture was heated to reflux for two hours The mixture was cooled the solvent removed in vacuo 20 mL of EtOAc and the resulting solution was washed with 2×100 mL of 2N aqueous HCl and 60 mL of water The organic layer was dried over sodium sulfate filtered concentrated in vacuo The residue was purified by flash chromatography on 210 g of silica gel with 2 liters of 3:1 hexanes CH2Cl2

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

Procedure: To a solution of 15.2 g (125 mmole) of 3,5dimethylaniline in 60 mL of toluene was added 15 g (146 mmole) of acetic anhydride, whereupon the internal temperature rose to 75° C. The mixture was allowed to cool to room temperature and the solvent was removed in vacuo. The residue was dissolved in 150 mL of hot ethyl acetate and the solution allowed to stand for 16 hours. The resulting mixture was cooled at 5° C. for 3 hours and the solid collected by filtration to give 18.43 g (90%) of off-white crystals. rose to 75° C the solvent was removed in vacuo The residue was dissolved in 150 mL of hot ethyl acetate The resulting mixture was cooled at 5° C. for 3 hours the solid collected by filtration

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

Procedure: To a solution of 15.2 g (125 mmole) of 3,5dimethylaniline in 60 mL of toluene was added 15 g (146 mmole) of acetic anhydride, whereupon the internal temperature rose to 75° C. The mixture was allowed to cool to room temperature and the solvent was removed in vacuo. The residue was dissolved in 150 mL of hot ethyl acetate and the solution allowed to stand for 16 hours. The resulting mixture was cooled at 5° C. for 3 hours and the solid collected by filtration to give 18.43 g (90%) of off-white crystals. rose to 75° C the solvent was removed in vacuo The residue was dissolved in 150 mL of hot ethyl acetate The resulting mixture was cooled at 5° C. for 3 hours the solid collected by filtration

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

Procedure: To a solution of 15.2 g (125 mmole) of 3,5dimethylaniline in 60 mL of toluene was added 15 g (146 mmole) of acetic anhydride, whereupon the internal temperature rose to 75° C. The mixture was allowed to cool to room temperature and the solvent was removed in vacuo. The residue was dissolved in 150 mL of hot ethyl acetate and the solution allowed to stand for 16 hours. The resulting mixture was cooled at 5° C. for 3 hours and the solid collected by filtration to give 18.43 g (90%) of off-white crystals. rose to 75° C the solvent was removed in vacuo The residue was dissolved in 150 mL of hot ethyl acetate The resulting mixture was cooled at 5° C. for 3 hours the solid collected by filtration

Conditions: temp:175.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 9.6 g (58.8 mmole) of N-acetyl-3,5-dimethylaniline, 8.13 g (58.8 mmole) of potassium carbonate (dried at 155° C. under vacuum), 23 g (147 mmole) of bromobenzene (dried over molecular sieves), and 1.12 g (5.9 mmole) of cuprous iodide was heated in a 175° C. oil bath under a reflux condenser under nitrogen for 18 hours. The mixture was cooled to room temperature and triturated with 1 liter of benzene. The solution was concentrated in vacuo. The residue was treated with 60 mL of EtOH and 7.76 g (118 mmole) of potassium hydroxide and the resulting mixture was heated to reflux for two hours. The mixture was cooled and the solvent removed in vacuo. The residue was taken up in 150 mL of hexanes and 20 mL of EtOAc and the resulting solution was washed with 2×100 mL of 2N aqueous HCl and 60 mL of water. The organic layer was dried over sodium sulfate, filtered and concentrated in vacuo. The residue was purified by flash chromatography on 210 g of silica gel with 2 liters of 3:1 hexanes CH2Cl2 to give 5.5 g (47%) of a light red oil. The mixture was cooled to room temperature triturated with 1 liter of benzene The solution was concentrated in vacuo the resulting mixture was heated to reflux for two hours The mixture was cooled the solvent removed in vacuo 20 mL of EtOAc and the resulting solution was washed with 2×100 mL of 2N aqueous HCl and 60 mL of water The organic layer was dried over sodium sulfate filtered concentrated in vacuo The residue was purified by flash chromatography on 210 g of silica gel with 2 liters of 3:1 hexanes CH2Cl2

Conditions: temp:175.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 9.6 g (58.8 mmole) of N-acetyl-3,5-dimethylaniline, 8.13 g (58.8 mmole) of potassium carbonate (dried at 155° C. under vacuum), 23 g (147 mmole) of bromobenzene (dried over molecular sieves), and 1.12 g (5.9 mmole) of cuprous iodide was heated in a 175° C. oil bath under a reflux condenser under nitrogen for 18 hours. The mixture was cooled to room temperature and triturated with 1 liter of benzene. The solution was concentrated in vacuo. The residue was treated with 60 mL of EtOH and 7.76 g (118 mmole) of potassium hydroxide and the resulting mixture was heated to reflux for two hours. The mixture was cooled and the solvent removed in vacuo. The residue was taken up in 150 mL of hexanes and 20 mL of EtOAc and the resulting solution was washed with 2×100 mL of 2N aqueous HCl and 60 mL of water. The organic layer was dried over sodium sulfate, filtered and concentrated in vacuo. The residue was purified by flash chromatography on 210 g of silica gel with 2 liters of 3:1 hexanes CH2Cl2 to give 5.5 g (47%) of a light red oil. The mixture was cooled to room temperature triturated with 1 liter of benzene The solution was concentrated in vacuo the resulting mixture was heated to reflux for two hours The mixture was cooled the solvent removed in vacuo 20 mL of EtOAc and the resulting solution was washed with 2×100 mL of 2N aqueous HCl and 60 mL of water The organic layer was dried over sodium sulfate filtered concentrated in vacuo The residue was purified by flash chromatography on 210 g of silica gel with 2 liters of 3:1 hexanes CH2Cl2

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

Procedure: To a solution of 15.2 g (125 mmole) of 3,5-dimethylaniline in 60 mL of toluene was added 15 g (146 mmole) of acetic anhydride, whereupon the internal temperature rose to 75° C. The mixture was allowed to cool to room temperature and the solvent was removed in vacuo. The residue was dissolved in 150 mL of hot ethyl acetate and the solution allowed to stand for 16 hours. The resulting mixture was cooled at 5° C. for 3 hours and the solid collected by filtration to give 18.43 g (90%) of off-white crystals. rose to 75° C the solvent was removed in vacuo The residue was dissolved in 150 mL of hot ethyl acetate The resulting mixture was cooled at 5° C. for 3 hours the solid collected by filtration

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

Procedure: Benzyltrimethylammonium tribromide (BTMA-Br3) (7.8 g, 20.21 mmol) was added to a solution of N-(3,5-dimethyl-phenyl)-acetamide (3.0 g, 18.38 mmol) in CH2Cl2/MeOH (90 ml/90 ml) at room temperature in an Ar atmosphere. The reaction mixture was stirred at room temperature for 10 minutes. The reaction mixture was concentrated under reduced pressure, and CH2Cl2 was then added to the resulting residue. The organic layer was washed with H2O, and then dried over anhydrous Na2SO4 and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:EtOAc=1:1) to give N-(4-bromo-3,5-dimethyl-phenyl)-acetamide (4.0 g, yield 90%). The reaction mixture was concentrated under reduced pressure, and CH2Cl2 was then added to the resulting residue The organic layer was washed with H2O dried over anhydrous Na2SO4 concentrated under reduced pressure The residue was purified by silica gel column chromatography (hexane:EtOAc=1:1)