5-bromo-2-(bromomethyl)-1,3-difluorobenzene

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 5-bromo-2-(bromomethyl)-1,3-difluorobenzene (1.6 g, 5.60 mmol) in DMF (20 mL) was added KCN (0.401 g, 6.16 mmol). The resulting mixture was stirred at 25° C. for 16 h. The mixture was dissolved in H2O (50 mL) and extracted by EA (50 mL). The organic layer was dried over Na2SO4, filtered and concentrated. The crude material was purified by silica column chromatography (PE/EA=3/1) to yield a white solid of 2-(4-bromo-2,6-difluorophenyl)acetonitrile (1.1 g, 2.57 mmol, 45.9% yield): 1H NMR (400 MHz, CD3OD) δ 7.39-7.36 (m, 2H), 3.89 (s, 2H). extracted by EA (50 mL) The organic layer was dried over Na2SO4 filtered concentrated The crude material was purified by silica column chromatography (PE/EA=3/1)

反応条件: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 5-bromo-2-(bromomethyl)-1,3-difluorobenzene (1.6 g, 5.60 mmol) in DMF (20 mL) was added KCN (0.401 g, 6.16 mmol). The resulting mixture was stirred at 25° C. for 16 h. The mixture was dissolved in H2O (50 mL) and extracted by EA (50 mL). The organic layer was dried over Na2SO4, filtered and concentrated. The crude material was purified by silica column chromatography (PE/EA=3/1) to yield a white solid of 2-(4-bromo-2,6-difluorophenyl)acetonitrile (1.1 g, 2.57 mmol, 45.9% yield): 1H NMR (400 MHz, CD3OD) δ 7.39-7.36 (m, 2H), 3.89 (s, 2H). extracted by EA (50 mL) The organic layer was dried over Na2SO4 filtered concentrated The crude material was purified by silica column chromatography (PE/EA=3/1)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of (4-bromo-2,6-difluorophenyl)methanol (2 g, 8.97 mmol) in DCM (80 mL) was added tribromophosphine (2.91 g, 10.76 mmol) at 0° C. The resulting mixture was stirred at rt. After LCMS analysis showed the starting material had disappeared, the mixture was washed with aqueous NaHCO3 (40 mL) and brine (30 mL). The organic layer was dried over Na2SO4, filtered and concentrated. The crude material was purified by silica column chromatography (PE/EA=5/1) to yield a colorless oil of 5-bromo-2-(bromomethyl)-1,3-difluorobenzene (1.6 g, 5.48 mmol, 61.2% yield): 1H NMR (400 MHz, CD3OD) δ 7.12 (d, J=6.8 Hz, 2H), 4.47 (s, 2H). the mixture was washed with aqueous NaHCO3 (40 mL) and brine (30 mL) The organic layer was dried over Na2SO4 filtered concentrated The crude material was purified by silica column chromatography (PE/EA=5/1)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 5-Bromo-2-hydroxymethyl-1,3-difluoro-benzene (0.89 g, 4.0 mmol) and 30 wt % of hydrogen bromide in acetic acid was stirred at room temperature for 90 minutes before it was poured into 80 ml of water. The mixture was extracted with pentane (3×50 ml) and the combined organic layers were washed with water (3×20 ml), dried over MgSO4 and concentrated at low pressure to afford the desired product (10.0 g, 98% yield). 1H NMR (CDCl3) δ: 4.47 (s, 2H), 7.09–7.10 (m, 1H), 7.12–7.13 (m, 1H). The mixture was extracted with pentane (3×50 ml) the combined organic layers were washed with water (3×20 ml) dried over MgSO4 concentrated at low pressure

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 5-Bromo-2-hydroxymethyl-1,3-difluoro-benzene (0.89 g, 4.0 mmol) and 30 wt % of hydrogen bromide in acetic acid was stirred at room temperature for 90 minutes before it was poured into 80 ml of water. The mixture was extracted with pentane (3×50 ml) and the combined organic layers were washed with water (3×20 ml), dried over MgSO4 and concentrated at low pressure to afford the desired product (10.0 g, 98% yield). 1H NMR (CDCl3) δ: 4.47 (s, 2H), 7.09–7.10 (m, 1H), 7.12–7.13 (m, 1H). The mixture was extracted with pentane (3×50 ml) the combined organic layers were washed with water (3×20 ml) dried over MgSO4 concentrated at low pressure

反応条件: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 5-bromo-2-(bromomethyl)-1,3-difluorobenzene (1.6 g, 5.60 mmol) in DMF (20 mL) was added KCN (0.401 g, 6.16 mmol). The resulting mixture was stirred at 25° C. for 16 h. The mixture was dissolved in H2O (50 mL) and extracted by EA (50 mL). The organic layer was dried over Na2SO4, filtered and concentrated. The crude material was purified by silica column chromatography (PE/EA=3/1) to yield a white solid of 2-(4-bromo-2,6-difluorophenyl)acetonitrile (1.1 g, 2.57 mmol, 45.9% yield): 1H NMR (400 MHz, CD3OD) δ 7.39-7.36 (m, 2H), 3.89 (s, 2H). extracted by EA (50 mL) The organic layer was dried over Na2SO4 filtered concentrated The crude material was purified by silica column chromatography (PE/EA=3/1)

反応条件: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 5-bromo-2-(bromomethyl)-1,3-difluorobenzene (1.6 g, 5.60 mmol) in DMF (20 mL) was added KCN (0.401 g, 6.16 mmol). The resulting mixture was stirred at 25° C. for 16 h. The mixture was dissolved in H2O (50 mL) and extracted by EA (50 mL). The organic layer was dried over Na2SO4, filtered and concentrated. The crude material was purified by silica column chromatography (PE/EA=3/1) to yield a white solid of 2-(4-bromo-2,6-difluorophenyl)acetonitrile (1.1 g, 2.57 mmol, 45.9% yield): 1H NMR (400 MHz, CD3OD) δ 7.39-7.36 (m, 2H), 3.89 (s, 2H). extracted by EA (50 mL) The organic layer was dried over Na2SO4 filtered concentrated The crude material was purified by silica column chromatography (PE/EA=3/1)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of (4-bromo-2,6-difluorophenyl)methanol (2 g, 8.97 mmol) in DCM (80 mL) was added tribromophosphine (2.91 g, 10.76 mmol) at 0° C. The resulting mixture was stirred at rt. After LCMS analysis showed the starting material had disappeared, the mixture was washed with aq NaHCO3 (40 mL) and brine (30 mL). The organic layer was dried over Na2SO4, filtered and concentrated. The crude material was purified by silica column chromatography (PE/EA=5/1) to yield a colorless oil of 5-bromo-2-(bromomethyl)-1,3-difluorobenzene (1.6 g, 5.48 mmol, 61.2% yield): 1H NMR (400 MHz, CD3OD) δ 7.12 (d, J=6.8 Hz, 2H), 4.47 (s, 2H). the mixture was washed with aq NaHCO3 (40 mL) and brine (30 mL) The organic layer was dried over Na2SO4 filtered concentrated The crude material was purified by silica column chromatography (PE/EA=5/1)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a cooled (0° C.) solution of 4 g (17.6 mmol) 4-bromo-2,6-difluorobenzyl alcohol in 50 ml THF, 7 g (26.4 mmol) triphenylphosphine and 8.83 g (26.4 mmol) carbon tetrabromide are added with stirring. Stirring is continued for 10 min at 0° C. and for 1 h at room temperature. After that the reaction mixture is filtered and the filtrate is concentrated in vacuo. The residue is purified by chromatography (silicagel, hexane) to afford the title compound as yellowish oil. are added Stirring After that the reaction mixture is filtered the filtrate is concentrated in vacuo The residue is purified by chromatography (silicagel, hexane)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 3.8 g (11.3 mmol) 5-bromo-2-bromomethyl-1,3-difluoro-benzene, 1.83 g (13.6 mmol) thiomorpholine dioxide and 1.88 ml (13.6 mmol) triethylamine in 40 ml dichloromethane is stirred at room temperature for 20 h. Then the reaction mixture is poured on water and extracted 3× with EtOAc. The combined organic layers are washed with water and saturated NaCl solution, dried over MgSO4, filtered and the filtrate is concentrated in vacuo. The residue is taken up in diethylether, vigorously stirred, and the title compound is obtained after filtration as a white crystalline solid. Then the reaction mixture is poured on water extracted 3× with EtOAc The combined organic layers are washed with water and saturated NaCl solution dried over MgSO4 filtered the filtrate is concentrated in vacuo

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 3.8 g (11.3 mmol) 5-bromo-2-bromomethyl-1,3-difluoro-benzene, 1.83 g (13.6 mmol) thiomorpholine dioxide and 1.88 ml (13.6 mmol) triethylamine in 40 ml dichloromethane is stirred at room temperature for 20 h. Then the reaction mixture is poured on water and extracted 3× with EtOAc. The combined organic layers are washed with water and saturated NaCl solution, dried over MgSO4, filtered and the filtrate is concentrated in vacuo. The residue is taken up in diethylether, vigorously stirred, and the title compound is obtained after filtration as a white crystalline solid. Then the reaction mixture is poured on water extracted 3× with EtOAc The combined organic layers are washed with water and saturated NaCl solution dried over MgSO4 filtered the filtrate is concentrated in vacuo