4-chloro-N-(4-chloro-2-methylphenyl)benzamide

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

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

Procedure: n-Butyllithium (1.6M in hexanes, 127 mL, 203 mmol) was added dropwise to a stirred, cooled (−10° C.) solution of 4-chloro-N-(4-chloro-2-methylphenyl)benzamide (Description 27, 27.1 g, 97 mmol) in tetrahydrofuran (600 mL). The mixture was allowed to warm to room temperature and stirred overnight. The mixture was cooled to 0° C. and further n-butyllithium (1.6M in hexanes, 30 mL, 483 mmol) was added dropwise. The mixture was stirred at room temperature for 2 h., then hydrochloric acid (2.5M, 200 mL) was added. The mixture was stirred at room temperature overnight, then extracted with ethyl acetate. The combined organic fractions were dried (MgSO4) and the solvent was evaporated under reduced pressure. The residue was purified by flash column chromatography on silica gel, eluting with isohexane/EtOAc (85:15), to give the title compound (3.6 g, 14%). 1H NMR (360 MHz, CDCl3) δ 8.30 (1H, br s), 7.57 (3H, m), 7.42 (2H, d, J 9.1 Hz), 7.30 (1H, d, J 8.6 Hz), 7.15 (1H, dd, J 8.6, 2.0 Hz) and 6.74 (1H, s). The mixture was cooled to 0° C. The mixture was stirred at room temperature for 2 h. The mixture was stirred at room temperature overnight extracted with ethyl acetate The combined organic fractions were dried (MgSO4) the solvent was evaporated under reduced pressure The residue was purified by flash column chromatography on silica gel eluting with isohexane/EtOAc (85:15)

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

Procedure: n-Butyllithium (1.6M in hexanes, 127 mL, 203 mmol) was added dropwise to a stirred, cooled (−10° C.) solution of 4-chloro-N-(4-chloro-2-methylphenyl)benzamide (Description 27, 27.1 g, 97 mmol) in tetrahydrofuran (600 mL). The mixture was allowed to warm to room temperature and stirred overnight. The mixture was cooled to 0° C. and further n-butyllithium (1.6M in hexanes, 30 mL, 483 mmol) was added dropwise. The mixture was stirred at room temperature for 2 h., then hydrochloric acid (2.5M, 200 mL) was added. The mixture was stirred at room temperature overnight, then extracted with ethyl acetate. The combined organic fractions were dried (MgSO4) and the solvent was evaporated under reduced pressure. The residue was purified by flash column chromatography on silica gel, eluting with isohexane/EtOAc (85:15), to give the title compound (3.6 g, 14%). 1H NMR (360 MHz, CDCl3) δ 8.30 (1H, br s), 7.57 (3H, m), 7.42 (2H, d, J 9.1 Hz), 7.30 (1H, d, J 8.6 Hz), 7.15 (1H, dd, J 8.6, 2.0 Hz) and 6.74 (1H, s). The mixture was cooled to 0° C. The mixture was stirred at room temperature for 2 h. The mixture was stirred at room temperature overnight extracted with ethyl acetate The combined organic fractions were dried (MgSO4) the solvent was evaporated under reduced pressure The residue was purified by flash column chromatography on silica gel eluting with isohexane/EtOAc (85:15)

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

Procedure: 4-Chlorobenzoyl chloride (19.5 g, 111 mmol) was added over 10 min. to a stirred, cooled (0° C.) solution of 4-chloro-2-methylaniline (15 g, 106 mmol) and triethylamine (22.2 mL, 16.1 g, 159 mmol) in dichloromethane (300 mL) and the mixture was stirred at room temperature for 2 h. Water (100 mL) was added and the dichloromethane was evaporated under reduced pressure. Aqueous sodium hydrogen carbonate (saturated, 200 mL), water (200 mL) and ethyl acetate (1000 mL) were added and the layers were separated. The organic layer was dried (MgSO4) and the solvent was evaporated under reduced pressure. The residue was triturated with ether and the solid was collected and dried in vacuo to give the title compound (27.3 g, 92%). 1H NMR (360 MHz, CDCl3) δ 7.82 (3H, m), 7.79 (1H, br s), 7.48 (2H, d, J 8.5 Hz), 7.23 (2H, m), and 2.30 (3H, s). the dichloromethane was evaporated under reduced pressure Aqueous sodium hydrogen carbonate (saturated, 200 mL), water (200 mL) and ethyl acetate (1000 mL) were added the layers were separated The organic layer was dried (MgSO4) the solvent was evaporated under reduced pressure The residue was triturated with ether the solid was collected dried in vacuo

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

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

Procedure: n-Butyllithium (1.6M in hexanes, 127 mL, 203 mmol) was added dropwise to a stirred, cooled (−10° C.) solution of 4-chloro-N-(4-chloro-2-methylphenyl)benzamide (Description 27, 27.1 g, 97 mmol) in tetrahydrofuran (600 mL). The mixture was allowed to warm to room temperature and stirred overnight. The mixture was cooled to 0° C. and further n-butyllithium (1.6M in hexanes, 30 mL, 483 mmol) was added dropwise. The mixture was stirred at room temperature for 2 h., then hydrochloric acid (2.5M, 200 mL) was added. The mixture was stirred at room temperature overnight, then extracted with ethyl acetate. The combined organic fractions were dried (MgSO4) and the solvent was evaporated under reduced pressure. The residue was purified by flash column chromatography on silica gel, eluting with isohexane/EtOAc (85:15), to give the title compound (3.6 g, 14%). 1H NMR (360 MHz, CDCl3) δ 8.30 (1H, br s), 7.57 (3H, m), 7.42 (2H, d, J 9.1 Hz), 7.30 (1H, d, J 8.6 Hz), 7.15 (1H, dd, J 8.6, 2.0 Hz) and 6.74 (1H, s). The mixture was cooled to 0° C. The mixture was stirred at room temperature for 2 h. The mixture was stirred at room temperature overnight extracted with ethyl acetate The combined organic fractions were dried (MgSO4) the solvent was evaporated under reduced pressure The residue was purified by flash column chromatography on silica gel eluting with isohexane/EtOAc (85:15)

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

Procedure: 4-Chlorobenzoyl chloride (19.5 g, 111 mmol) was added over 10 min. to a stirred, cooled (0° C.) solution of 4-chloro-2-methylaniline (15 g, 106 mmol) and triethylamine (22.2 mL, 16.1 g, 159 mmol) in dichloromethane (300 mL) and the mixture was stirred at room temperature for 2 h. Water (100 mL) was added and the dichloromethane was evaporated under reduced pressure. Aqueous sodium hydrogen carbonate (saturated, 200 mL), water (200 mL) and ethyl acetate (1000 mL) were added and the layers were separated. The organic layer was dried (MgSO4) and the solvent was evaporated under reduced pressure. The residue was triturated with ether and the solid was collected and dried in vacuo to give the title compound (27.3 g, 92%). 1H NMR (360 MHz, CDCl3) δ 7.82 (3H, m), 7.79 (1H, br s), 7.48 (2H, d, J 8.5 Hz), 7.23 (2H, m), and 2.30 (3H, s). the dichloromethane was evaporated under reduced pressure Aqueous sodium hydrogen carbonate (saturated, 200 mL), water (200 mL) and ethyl acetate (1000 mL) were added the layers were separated The organic layer was dried (MgSO4) the solvent was evaporated under reduced pressure The residue was triturated with ether the solid was collected dried in vacuo