1-(4-amino-2,6-dimethylphenyl)ethanone

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 1-(4-amino-2,6-dimethylphenyl)ethanone (3.26 g, 20.0 mmol), K3PO4 (9.2 g, 40 mmol), and 1-iodobenzene (4.08 g, 20.0 mmol) in DMF (35.0 mL) was added CuI (761.8 mg, 40 mmol). The reaction was heated at 110° C. overnight under N2. The solution was cooled to room temperature and filtered through a small pad of Celite. The cake was washed with ethyl acetate (50 mL) and the combined filtrate was concentrated under reduced pressure. The residue was purified by flash column chromatography on silica gel to give 1-(2,6-dimethyl-4-(phenylamino)phenyl)ethanone as red-brown syrup: 1H NMR (500 MHz, CDCl3) δ 7.30 (d, J=8.2 Hz, 2 H), 7.10 (d, J=7.7 Hz, 2 H), 6.99 (d, J=4.2 Hz, 1 H), 6.71 (s, 1 H), 2.47 (s, 3 H), 2.18 (s, 6 H); ESI-MS: m/z 239.5 (M+H)+. The solution was cooled to room temperature filtered through a small pad of Celite The cake was washed with ethyl acetate (50 mL) the combined filtrate was concentrated under reduced pressure The residue was purified by flash column chromatography on silica gel

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

Procedure: Anhydrous copper(II) chloride (98.9 g, 0.74 mol) was mixed with tert-butyl nitrite (94.8 g, 0.83 mol) in acetonitrile (1.02 L). The solution was cooled to 0° C. and slowly added with 1-(4-amino-2,6-dimethylphenyl)ethanone (100 g, 0.61 mol) in a period of 5.0 min. After the addition was completed, the reaction mixture was warmed to room temperature, and was poured into an aqueous hydrochloric acid solution (20%, 1.0 L). The solution was extracted with EtOAc (800 mL), and the organic layer was separated, washed with H2O (1.0 L), dried over MgSO4 (s), and concentrated under reduced pressure. The liquid was distilled to give 1-(4-chloro-2,6-dimethylphenyl)ethanone (85.0 g) as yellow oil in 76% yield: 1H NMR (500 MHz, CDCl3) δ 7.02 (s, 2 H), 2.45 (s, 3 H), 2.22 (s, 6 H). After the addition the reaction mixture was warmed to room temperature The solution was extracted with EtOAc (800 mL) the organic layer was separated washed with H2O (1.0 L) dried over MgSO4 (s) concentrated under reduced pressure The liquid was distilled

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 1-(4-amino-2,6-dimethylphenyl)ethanone (3.26 g, 20.0 mmol), K3PO4 (9.2 g, 40 mmol), and 1-iodobenzene (4.08 g, 20.0 mmol) in DMF (35.0 mL) was added CuI (761.8 mg, 40 mmol). The reaction was heated at 110° C. overnight under N2. The solution was cooled to room temperature and filtered through a small pad of Celite. The cake was washed with ethyl acetate (50 mL) and the combined filtrate was concentrated under reduced pressure. The residue was purified by flash column chromatography on silica gel to give 1-(2,6-dimethyl-4-(phenylamino)phenyl)ethanone as red-brown syrup: 1H NMR (500 MHz, CDCl3) δ 7.30 (d, J=8.2 Hz, 2H), 7.10 (d, J=7.7 Hz, 2H), 6.99 (d, J=4.2 Hz, 1H), 6.71 (s, 1H), 2.47 (s, 3H), 2.18 (s, 6H); ESI-MS: m/z 239.5 (M+H)+. The solution was cooled to room temperature filtered through a small pad of Celite The cake was washed with ethyl acetate (50 mL) the combined filtrate was concentrated under reduced pressure The residue was purified by flash column chromatography on silica gel

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

Procedure: Anhydrous copper(II) chloride (98.9 g, 0.74 mol) was mixed with tert-butyl nitrite (94.8 g, 0.83 mol) in acetonitrile (1.02 L). The solution was cooled to 0° C. and slowly added with 1-(4-amino-2,6-dimethylphenyl)ethanone (100 g, 0.61 mol) in a period of 5.0 min. After the addition was completed, the reaction mixture was warmed to room temperature, and was poured into an aqueous hydrochloric acid solution (20%, 1.0 L). The solution was extracted with EtOAc (800 mL), and the organic layer was separated, washed with H2O (1.0 L), dried over MgSO4 (s), and concentrated under reduced pressure. The liquid was distilled to give 1-(4-chloro-2,6-dimethylphenyl)ethanone (85.0 g) as yellow oil in 76% yield: 1H NMR (500 MHz, CDCl3) δ 7.02 (s, 2H), 2.45 (s, 3H), 2.22 (s, 6H). After the addition the reaction mixture was warmed to room temperature The solution was extracted with EtOAc (800 mL) the organic layer was separated washed with H2O (1.0 L) dried over MgSO4 (s) concentrated under reduced pressure The liquid was distilled

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 1-(4-amino-2,6-dimethylphenyl)ethanone (3.26 g, 20.0 mmol), K3PO4 (9.2 g, 40 mmol), and 1-iodobenzene (4.08 g, 20.0 mmol) in DMF (35.0 mL) was added CuI (761.8 mg, 40 mmol). The reaction was heated at 110° C. overnight under N2. The solution was cooled to room temperature and filtered through a small pad of diatomaceous earth. The cake was washed with ethyl acetate (50 mL) and the combined filtrate was concentrated under reduced pressure. The residue was purified by flash column chromatography on silica gel to give 1-(2,6-dimethyl-4-(phenylamino)phenyl)ethanone as red-brown syrup: 1H NMR (500 MHz, CDCl3) δ 7.30 (d, J=8.2 Hz, 2 H), 7.10 (d, J=7.7 Hz, 2 H), 6.99 (d, J=4.2 Hz, 1 H), 6.71 (s, 1 H), 2.47 (s, 3 H), 2.18 (s, 6 H); ESI-MS: m/z 239.5 (M+H)+. The solution was cooled to room temperature filtered through a small pad of diatomaceous earth The cake was washed with ethyl acetate (50 mL) the combined filtrate was concentrated under reduced pressure The residue was purified by flash column chromatography on silica gel

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

Procedure: Anhydrous copper(II) chloride (98.9 g, 0.74 mol) was mixed with tert-butyl nitrite (94.8 g, 0.83 mol) in acetonitrile (1.02 L). The solution was cooled to 0° C. and slowly added with 1-(4-amino-2,6 dimethylphenyl)ethanone (100 g, 0.61 mol) in a period of 5.0 min. After the addition was completed, the reaction mixture was warmed to room temperature, and was poured into an aqueous hydrochloric acid solution (20%, 1.0 L). The solution was extracted with EtOAc (800 mL), and the organic layer was separated, washed with H2O (1.0 L), dried over MgSO4 (s), and concentrated under reduced pressure. The liquid was distilled to give 1-(4-chloro-2,6-dimethylphenyl)ethanone (85.0 g) as yellow oil in 76% yield: 1H NMR (500 MHz, CDCl3) δ 7.02 (s, 2 H), 2.45 (s, 3 H), 2.22 (s, 6 H). After the addition the reaction mixture was warmed to room temperature The solution was extracted with EtOAc (800 mL) the organic layer was separated washed with H2O (1.0 L) dried over MgSO4 (s) concentrated under reduced pressure The liquid was distilled