5-溴-2-(二氟甲氧基)甲苯

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To 4-bromo-1-(difluoromethoxy)-2-methylbenzene (2.36 g, 10.00 mmol) in toluene (50 mL) was added cis-2,6-dimethylpiperazine (5 g, 58.14 mmol), Pd(OAc)2 (120 mg, 0.53 mmol), BINAP (380 mg, 0.61 mmol), and t-BuOK (2.2 g, 19.64 mmol). The resulting solution was stirred for 4 hours at 80° C. The solution was cooled to room temperature and washed with H2O (2×50 mL), dried over Na2SO4, concentrated, and purified by silica gel column chromatography (10:1 CH2Cl2/MeOH) to give 1.1 g (41%) of 1-(4-(difluoromethoxy)-3-methylphenyl)-3,5-dimethylpiperazine. The solution was cooled to room temperature washed with H2O (2×50 mL) dried over Na2SO4 concentrated purified by silica gel column chromatography (10:1 CH2Cl2/MeOH)

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a stirred solution of 4-amino-1-difluoromethoxy-2-methyl-benzene (5 g, 28.90 mmol) in HBr (20 mL) and water (20 mL) at 0° C. was added a solution of sodium nitrite (2.07 g, 30.00 mmol) in H2O (10 ml) dropwise over a period of 20 minutes. After the addition was complete, the reaction mixture was stirred for 30 minutes at 0° C. Copper (I) bromide (4 g, 27.87 mmol) was then added and the mixture was heated at 60° C. for 30 minutes. The resulting solution was extracted with EtOAc (3×50 mL) and the combined organic layers washed with H2O (1×20 mL), dried over Na2SO4 and concentrated to provide 2.5 g (37%) of 4-bromo-1-(difluoromethoxy)-2-methylbenzene. After the addition the mixture was heated at 60° C. for 30 minutes The resulting solution was extracted with EtOAc (3×50 mL) the combined organic layers washed with H2O (1×20 mL) dried over Na2SO4 concentrated

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a stirred solution of 4-amino-1-difluoromethoxy-2-methyl-benzene (5 g, 28.90 mmol) in HBr (20 mL) and water (20 mL) at 0° C. was added a solution of sodium nitrite (2.07 g, 30.00 mmol) in H2O (10 ml) dropwise over a period of 20 minutes. After the addition was complete, the reaction mixture was stirred for 30 minutes at 0° C. Copper (I) bromide (4 g, 27.87 mmol) was then added and the mixture was heated at 60° C. for 30 minutes. The resulting solution was extracted with EtOAc (3×50 mL) and the combined organic layers washed with H2O (1×20 mL), dried over Na2SO4 and concentrated to provide 2.5 g (37%) of 4-bromo-1-(difluoromethoxy)-2-methylbenzene. After the addition the mixture was heated at 60° C. for 30 minutes The resulting solution was extracted with EtOAc (3×50 mL) the combined organic layers washed with H2O (1×20 mL) dried over Na2SO4 concentrated

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To 4-bromo-1-(difluoromethoxy)-2-methylbenzene (2.36 g, 10.00 mmol) in toluene (50 mL) was added cis-2,6-dimethylpiperazine (5 g, 58.14 mmol), Pd(OAc)2 (120 mg, 0.53 mmol), BINAP (380 mg, 0.61 mmol), and t-BuOK (2.2 g, 19.64 mmol). The resulting solution was stirred for 4 hours at 80° C. The solution was cooled to room temperature and washed with H2O (2×50 mL), dried over Na2SO4, concentrated, and purified by silica gel column chromatography (10:1 CH2Cl2/MeOH) to give 1.1 g (41%) of 1-(4-(difluoromethoxy)-3-methylphenyl)-3,5-dimethylpiperazine. The solution was cooled to room temperature washed with H2O (2×50 mL) dried over Na2SO4 concentrated purified by silica gel column chromatography (10:1 CH2Cl2/MeOH)

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a stirred solution of 4-amino-1-difluoromethoxy-2-methyl-benzene (5 g, 28.90 mmol) in HBr (20 mL) and water (20 mL) at 0° C. was added a solution of sodium nitrite (2.07 g, 30.00 mmol) in H2O (10 ml) dropwise over a period of 20 minutes. After the addition was complete, the reaction mixture was stirred for 30 minutes at 0° C. Copper (I) bromide (4 g, 27.87 mmol) was then added and the mixture was heated at 60° C. for 30 minutes. The resulting solution was extracted with EtOAc (3×50 mL) and the combined organic layers washed with H2O (1×20 mL), dried over Na2SO4 and concentrated to provide 2.5 g (37%) of 4-bromo-1-(difluoromethoxy)-2-methylbenzene. After the addition the mixture was heated at 60° C. for 30 minutes The resulting solution was extracted with EtOAc (3×50 mL) the combined organic layers washed with H2O (1×20 mL) dried over Na2SO4 concentrated

反应条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To 4-bromo-1-(difluoromethoxy)-2-methylbenzene (2.36 g, 10.00 mmol) in toluene (50 mL) was added cis-2,6-dimethylpiperazine (5 g, 58.14 mmol), Pd(OAc)2 (120 mg, 0.53 mmol), BINAP (380 mg, 0.61 mmol), and t-BuOK (2.2 g, 19.64 mmol). The resulting solution was stirred for 4 hours at 80° C. The solution was cooled to room temperature and washed with H2O (2×50 mL), dried over Na2SO4, concentrated, and purified by silica gel column chromatography (10:1 CH2Cl2/MeOH) to give 1.1 g (41%) of 1-(4-(difluoromethoxy)-3-methylphenyl)-3,5-dimethylpiperazine. The solution was cooled to room temperature washed with H2O (2×50 mL) dried over Na2SO4 concentrated purified by silica gel column chromatography (10:1 CH2Cl2/MeOH)