1-溴-2-乙基-5-氟-4-甲氧基苯

反应条件: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 1-bromo-2-ethyl-5-fluoro-4-methoxy-benzene (Preparation 12, 18.0 g, 77.2 mmol) in dioxane (100 mL) were added SPhos (4.12 g, 10.0 mmol), 4,4,5,5-tetramethyl-1,3,2-dioxaborolane (14.8 g, 116 mmol) and triethylamine (10.7 mL, 77.2 mmol). The reaction mixture was degassed with nitrogen prior to the addition of dichlorobis(acetonitrile)palladium (II) (801 mg, 3.09 mmol). The reaction mixture was then heated at 110° C. for 18 hours, cooled to room temperature and filtered through a pad of Celite, washing with EtOAc. The solvent was removed in vacuo and the residue was redissolved in EtOAc (30 mL) and washed with water (30 mL). The organic layer was dried over sodium sulfate and concentrated in vacuo. The crude material was triturated with methanol and the resulting solid was collected by filtration to give the title compound as a beige solid (13.8 g) in a 64% yield. The reaction mixture was degassed with nitrogen cooled to room temperature filtered through a pad of Celite washing with EtOAc The solvent was removed in vacuo the residue was redissolved in EtOAc (30 mL) washed with water (30 mL) The organic layer was dried over sodium sulfate concentrated in vacuo The crude material was triturated with methanol the resulting solid was collected by filtration

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

实验步骤: To a solution of 4-ethyl-1-fluoro-2-methoxy-benzene (WO 2010/090537, 12.2 g, 79.1 mmol) in MeCN (150 mL) was added a solution of NBS (14.4 g, 80.7 mmol) in MeCN (50 mL). The resulting solution was stirred at room temperature for 18 hours. The solvent was removed in vacuo and the residue was diluted with diethyl ether (150 mL). Precipitated solid was removed by filtration and the filtrate was washed with sodium sulfite aqueous solution (100 mL) and brine (100 mL), dried over MgSO4 and concentrated in vacuo to give the title compound as a yellow oil (18 g) in a 97% yield. The solvent was removed in vacuo the residue was diluted with diethyl ether (150 mL) Precipitated solid was removed by filtration the filtrate was washed with sodium sulfite aqueous solution (100 mL) and brine (100 mL) dried over MgSO4 concentrated in vacuo

反应条件: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 1-bromo-2-ethyl-5-fluoro-4-methoxy-benzene (Preparation 12, 18.0 g, 77.2 mmol) in dioxane (100 mL) were added SPhos (4.12 g, 10.0 mmol), 4,4,5,5-tetramethyl-1,3,2-dioxaborolane (14.8 g, 116 mmol) and triethylamine (10.7 mL, 77.2 mmol). The reaction mixture was degassed with nitrogen prior to the addition of dichlorobis(acetonitrile)palladium (II) (801 mg, 3.09 mmol). The reaction mixture was then heated at 110° C. for 18 hours, cooled to room temperature and filtered through a pad of Celite, washing with EtOAc. The solvent was removed in vacuo and the residue was redissolved in EtOAc (30 mL) and washed with water (30 mL). The organic layer was dried over sodium sulfate and concentrated in vacuo. The crude material was triturated with methanol and the resulting solid was collected by filtration to give the title compound as a beige solid (13.8 g) in a 64% yield. The reaction mixture was degassed with nitrogen cooled to room temperature filtered through a pad of Celite washing with EtOAc The solvent was removed in vacuo the residue was redissolved in EtOAc (30 mL) washed with water (30 mL) The organic layer was dried over sodium sulfate concentrated in vacuo The crude material was triturated with methanol the resulting solid was collected by filtration

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

实验步骤: To a solution of 4-ethyl-1-fluoro-2-methoxy-benzene (WO 2010/090537, 12.2 g, 79.1 mmol) in MeCN (150 mL) was added a solution of NBS (14.4 g, 80.7 mmol) in MeCN (50 mL). The resulting solution was stirred at room temperature for 18 hours. The solvent was removed in vacuo and the residue was diluted with diethyl ether (150 mL). Precipitated solid was removed by filtration and the filtrate was washed with sodium sulfite aqueous solution (100 mL) and brine (100 mL), dried over MgSO4 and concentrated in vacuo to give the title compound as a yellow oil (18 g) in a 97% yield. The solvent was removed in vacuo the residue was diluted with diethyl ether (150 mL) Precipitated solid was removed by filtration the filtrate was washed with sodium sulfite aqueous solution (100 mL) and brine (100 mL) dried over MgSO4 concentrated in vacuo

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

实验步骤: To a solution of 4-ethyl-1-fluoro-2-methoxy-benzene (WO 2010/090537, 12.2 g, 79.1 mmol) in MeCN (150 mL) was added a solution of NBS (14.4 g, 80.7 mmol) in MeCN (50 mL). The resulting solution was stirred at room temperature for 18 hours. The solvent was removed in vacuo and the residue was diluted with diethyl ether (150 mL). Precipitated solid was removed by filtration and the filtrate was washed with sodium sulfite aqueous solution (100 mL) and brine (100 mL), dried over MgSO4 and concentrated in vacuo to give the title compound as a yellow oil (18 g) in a 97% yield. The solvent was removed in vacuo the residue was diluted with diethyl ether (150 mL) Precipitated solid was removed by filtration the filtrate was washed with sodium sulfite aqueous solution (100 mL) and brine (100 mL) dried over MgSO4 concentrated in vacuo

反应条件: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 1-bromo-2-ethyl-5-fluoro-4-methoxy-benzene (Preparation 12, 18.0 g, 77.2 mmol) in dioxane (100 mL) were added SPhos (4.12 g, 10.0 mmol), 4,4,5,5-tetramethyl-1,3,2-dioxaborolane (14.8 g, 116 mmol) and triethylamine (10.7 mL, 77.2 mmol). The reaction mixture was degassed with nitrogen prior to the addition of dichlorobis(acetonitrile)palladium (II) (801 mg, 3.09 mmol). The reaction mixture was then heated at 110° C. for 18 hours, cooled to room temperature and filtered through a pad of Celite, washing with EtOAc. The solvent was removed in vacuo and the residue was redissolved in EtOAc (30 mL) and washed with water (30 mL). The organic layer was dried over sodium sulfate and concentrated in vacuo. The crude material was triturated with methanol and the resulting solid was collected by filtration to give the title compound as a beige solid (13.8 g) in a 64% yield. The reaction mixture was degassed with nitrogen cooled to room temperature filtered through a pad of Celite washing with EtOAc The solvent was removed in vacuo the residue was redissolved in EtOAc (30 mL) washed with water (30 mL) The organic layer was dried over sodium sulfate concentrated in vacuo The crude material was triturated with methanol the resulting solid was collected by filtration

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

实验步骤: To a solution of 4-ethyl-1-fluoro-2-methoxy-benzene (WO-2010/090537, 12.2 g, 79.1 mmol) in MeCN (150 mL) was added a solution of NBS (14.4 g, 80.7 mmol) in MeCN (50 mL). The resulting solution was stirred at room temperature for 18 hours. The solvent was removed in vacuo and the residue was diluted with diethyl ether (150 mL). Precipitated solid was removed by filtration and the filtrate was washed with sodium sulfite aqueous solution (100 mL) and brine (100 mL), dried over MgSO4 and concentrated in vacuo to give the title compound as a yellow oil (18 g) in a 97% yield. The solvent was removed in vacuo the residue was diluted with diethyl ether (150 mL) Precipitated solid was removed by filtration the filtrate was washed with sodium sulfite aqueous solution (100 mL) and brine (100 mL) dried over MgSO4 concentrated in vacuo

反应条件: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 1-bromo-2-ethyl-5-fluoro-4-methoxy-benzene (Preparation 12, 18.0 g, 77.2 mmol) in dioxane (100 mL) were added SPhos (4.12 g, 10.0 mmol), 4,4,5,5-tetramethyl-1,3,2-dioxaborolane (14.8 g, 116 mmol) and triethylamine (10.7 mL, 77.2 mmol). The reaction mixture was degassed with nitrogen prior to the addition of dichlorobis(acetonitrile)palladium (II) (801 mg, 3.09 mmol). The reaction mixture was then heated at 110° C. for 18 hours, cooled to room temperature and filtered through a pad of Celite, washing with EtOAc. The solvent was removed in vacuo and the residue was redissolved in EtOAc (30 mL) and washed with water (30 mL). The organic layer was dried over sodium sulfate and concentrated in vacuo. The crude material was triturated with methanol and the resulting solid was collected by filtration to give the title compound as a beige solid (13.8 g) in a 64% yield. The reaction mixture was degassed with nitrogen cooled to room temperature filtered through a pad of Celite washing with EtOAc The solvent was removed in vacuo the residue was redissolved in EtOAc (30 mL) washed with water (30 mL) The organic layer was dried over sodium sulfate concentrated in vacuo The crude material was triturated with methanol the resulting solid was collected by filtration

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

实验步骤: To a solution of 4-ethyl-1-fluoro-2-methoxy-benzene (WO 2010/090537, 12.2 g, 79.1 mmol) in MeCN (150 mL) was added a solution of NBS (14.4 g, 80.7 mmol) in MeCN (50 mL). The resulting solution was stirred at room temperature for 18 hours. The solvent was removed in vacuo and the residue was diluted with diethyl ether (150 mL). Precipitated solid was removed by filtration and the filtrate was washed with sodium sulfite aqueous solution (100 mL) and brine (100 mL), dried over MgSO4 and concentrated in vacuo to give the title compound as a yellow oil (18 g) in a 97% yield. The solvent was removed in vacuo the residue was diluted with diethyl ether (150 mL) Precipitated solid was removed by filtration the filtrate was washed with sodium sulfite aqueous solution (100 mL) and brine (100 mL) dried over MgSO4 concentrated in vacuo