3-bromo-5-ethoxy-1-oxidopyridin-1-ium

反応条件: temp:45.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 3-bromo-5-ethoxypyridine-1-oxide (40 g, 183 mmol) in DCM (200 mL) at 0° C. was slowly added POCl3 (159 mL, 1701 mmol) over 30 min. Then the resulting solution was warmed to 45° C. and stirred for 15 h. The mixture was concentrated and adjusted pH=9-10 with 10% NaOH solution, extracted with DCM (300 mL×2), dried over Na2SO4, filtered, and concentrated to give the crude product which was purified by silica column chromatography (10% EA: 90% PE, 800 g silica column). All fractions found to contain product by TLC (EA: PE=1:5, Rf=0.6) were combined and concentrated to yield an oil of 5-bromo-2-chloro-3-ethoxypyridine (30 g, 60.9 mmol, 33% yield): 1H NMR (400 MHz, CD3OD) δ 8.00-7.99 (d, J=2.0 Hz, 1H), 7.65-7.64 (d, J=2.0 Hz, 1H), 4.17-4.12 (m, 2H), 1.44 (t, J=7.0 Hz, 2H); ES-LCMS m/z 235 (M+H). at 0° C. over 30 min The mixture was concentrated adjusted pH=9-10 with 10% NaOH solution, extracted with DCM (300 mL×2) dried over Na2SO4 filtered concentrated to give the crude product which was purified by silica column chromatography (10% EA: 90% PE, 800 g silica column) concentrated

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

実験手順: To a solution of 3-bromo-5-ethoxypyridine (53 g, 262 mmol) in DCM (600 mL) at 0° C. was slowly added m-CPBA (67.9 g, 393 mmol) over 30 min. After the resulting solution was stirred for 15 h, the mixture was washed with Na2S2O3 solution and extracted with DCM (600 mL×2). The combined organic layer was washed with saturated NaHCO3 (300 mL), brine (300 mL), dried over Na2SO4, filtered, and concentrated to give 3-bromo-5-ethoxypyridine-1-oxide (40 g, 165 mmol, 63% yield): 1HNMR (400 MHz, CD3OD) δ 8.19-8.18 (m, 1H), 8.08-8.07 (m, 1H), 7.50-7.49 (m, 1H), 4.17-4.15 (d, J=8.8 Hz, 2H), 1.43 (t, J=7.0 Hz, 3H); ES-LCMS m/z 217 (M+H). at 0° C. over 30 min the mixture was washed with Na2S2O3 solution extracted with DCM (600 mL×2) The combined organic layer was washed with saturated NaHCO3 (300 mL), brine (300 mL) dried over Na2SO4 filtered concentrated

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

実験手順: To a solution of 3-bromo-5-ethoxypyridine (53 g, 262 mmol) in DCM (600 mL) at 0° C. was slowly added m-CPBA (67.9 g, 393 mmol) over 30 min. After the resulting solution was stirred for 15 h, the mixture was washed with Na2S2O3 solution and extracted with DCM (600 mL×2). The combined organic layer was washed with saturated NaHCO3 (300 mL), brine (300 mL), dried over Na2SO4, filtered, and concentrated to give 3-bromo-5-ethoxypyridine-1-oxide (40 g, 165 mmol, 63% yield): 1HNMR (400 MHz, CD3OD) δ 8.19-8.18 (m, 1H), 8.08-8.07 (m, 1H), 7.50-7.49 (m, 1H), 4.17-4.15 (d, J=8.8 Hz, 2H), 1.43 (t, J=7.0 Hz, 3H); ES-LCMS m/z 217 (M+H). at 0° C. over 30 min the mixture was washed with Na2S2O3 solution extracted with DCM (600 mL×2) The combined organic layer was washed with saturated NaHCO3 (300 mL), brine (300 mL) dried over Na2SO4 filtered concentrated

反応条件: temp:45.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 3-bromo-5-ethoxypyridine 1-oxide (40 g, 183 mmol) in DCM (200 mL) at 0° C. was slowly added POCl3 (159 mL, 1701 mmol) over 30 min. Then the resulting solution was warmed to 45° C. for 15 h. The mixture was concentrated and extracted with DCM (2×200 mL), dried over Na2SO4, filtered, and concentrated to give 5-bromo-2-chloro-3-ethoxypyridine (30 g, 60.9 mmol, 33.2% yield): 1H NMR (400 MHz, CD3OD) δ 8.00-7.99 (d, J=2.0 Hz, 1H), 7.65-7.64 (d, J=2.0 Hz, 1H), 4.17-4.12 (m, 2H), 1.44 (t, J=7.0 Hz, 2H); ES-LCMS m/z 235 (M+H). at 0° C. over 30 min The mixture was concentrated extracted with DCM (2×200 mL) dried over Na2SO4 filtered concentrated

反応条件: temp:45.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 3-bromo-5-ethoxypyridine 1-oxide (40 g, 183 mmol) in DCM (200 mL) at 0° C. was slowly added POCl3 (159 mL, 1701 mmol) over 30 min. Then the resulting solution was warmed to 45° C. for 15 h. The mixture was concentrated and extracted with DCM (2×200 mL), dried over Na2SO4, filtered, and concentrated to give 5-bromo-2-chloro-3-ethoxypyridine (30 g, 60.9 mmol, 33.2% yield): 1H NMR (400 MHz, CD3OD) δ 8.00-7.99 (d, J=2.0 Hz, 1H), 7.65-7.64 (d, J=2.0 Hz, 1H), 4.17-4.12 (m, 2H), 1.44 (t, J=7.0 Hz, 2H); ES-LCMS m/z 235 (M+H). at 0° C. over 30 min The mixture was concentrated extracted with DCM (2×200 mL) dried over Na2SO4 filtered concentrated

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

実験手順: To a solution of 3-bromo-5-ethoxypyridine (53 g, 262 mmol) in DCM (200 mL) at 0° C. was slowly added m-CPBA (67.9 g, 393 mmol) over 30 min. After the resulting solution was stirred for 15 h, the mixture was washed with NaS2O3 solution and extracted with DCM (2×300 mL), dried over Na2SO4, filtered, and the organic phase was concentrated to give 3-bromo-5-ethoxypyridine 1-oxide (40 g, 165 mmol, 62.9% yield): 1H NMR (400 MHz, CD3OD) δ 8.19-8.18 (m, 1H), 8.08-8.07 (m, 1H), 7.50-7.49 (m, 1H), 4.17-4.15 (d, J=8.8 Hz, 2H), 1.43 (t, J=7.0 Hz, 3H); ES-LCMS m/z 217 (M+H). at 0° C. over 30 min the mixture was washed with NaS2O3 solution extracted with DCM (2×300 mL) dried over Na2SO4 filtered the organic phase was concentrated

反応条件: temp:45.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 3-bromo-5-ethoxypyridine 1-oxide (40 g, 183 mmol) in DCM (200 mL) at 0° C. was slowly added POCl3 (159 mL, 1701 mmol) over 30 min. Then the resulting solution was warmed to 45° C. for 15 h. The mixture was concentrated and extracted with DCM (2×200 mL), dried over Na2SO4 and concentrated to give 5-bromo-2-chloro-3-ethoxypyridine (30 g, 60.9 mmol, 33.2% yield): 1H NMR (400 MHz, CD3OD) δ 8.00-7.99 (d, J=2.0 Hz, 1H), 7.65-7.64 (d, J=2.0 Hz, 1H), 4.17-4.12 (m, 2H), 1.44 (t, J=7.0 Hz, 2H); ES-LCMS m/z 235 (M+H). at 0° C. over 30 min The mixture was concentrated extracted with DCM (2×200 mL) dried over Na2SO4 concentrated

反応条件: temp:45.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 3-bromo-5-ethoxypyridine 1-oxide (40 g, 183 mmol) in DCM (200 mL) at 0° C. was slowly added POCl3 (159 mL, 1701 mmol) over 30 min. Then the resulting solution was warmed to 45° C. for 15 h. The mixture was concentrated and extracted with DCM (2×200 mL), dried over Na2SO4 and concentrated to give 5-bromo-2-chloro-3-ethoxypyridine (30 g, 60.9 mmol, 33.2% yield): 1H NMR (400 MHz, CD3OD) δ 8.00-7.99 (d, J=2.0 Hz, 1H), 7.65-7.64 (d, J=2.0 Hz, 1H), 4.17-4.12 (m, 2H), 1.44 (t, J=7.0 Hz, 2H); ES-LCMS m/z 235 (M+H). at 0° C. over 30 min The mixture was concentrated extracted with DCM (2×200 mL) dried over Na2SO4 concentrated

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

実験手順: To a solution of 3-bromo-5-ethoxypyridine (53 g, 262 mmol) in DCM (200 mL) at 0° C. was slowly added m-CPBA (67.9 g, 393 mmol) over 30 min. After the resulting solution was stirred for 15 h, the mixture was washed with NaS2O3 solution and extracted with DCM (2×300 mL), dried over Na2SO4 and the organic phase was concentrated to give 3-bromo-5-ethoxypyridine 1-oxide (40 g, 165 mmol, 62.9% yield): 1H NMR (400 MHz, CD3OD) δ 8.19-8.18 (m, 1H), 8.08-8.07 (m, 1H), 7.50-7.49 (m, 1H), 4.17-4.15 (d, J=8.8 Hz, 2H), 1.43 (t, J=7.0 Hz, 3H); ES-LCMS m/z 217 (M+H). at 0° C. over 30 min the mixture was washed with NaS2O3 solution extracted with DCM (2×300 mL) dried over Na2SO4 the organic phase was concentrated

反応条件: temp:45.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 3-bromo-5-ethoxypyridine 1-oxide (40 g, 183 mmol) in DCM (200 mL) at 0° C. was slowly added POCl3 (159 mL, 1701 mmol) over 30 min. Then the resulting solution was warmed to 45° C. for 15 h. The mixture was concentrated and extracted with DCM (2×200 mL), dried over Na2SO4 and concentrated to give 5-bromo-2-chloro-3-ethoxypyridine (30 g, 60.9 mmol, 33.2% yield): 1H NMR (400 MHz, CD3OD) δ 8.00-7.99 (d, J=2.0 Hz, 1H), 7.65-7.64 (d, J=2.0 Hz, 1H), 4.17-4.12 (m, 2H), 1.44 (t, J=7.0 Hz, 2H); ES-LCMS m/z 235 (M+H). at 0° C. over 30 min The mixture was concentrated extracted with DCM (2×200 mL) dried over Na2SO4 concentrated

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

実験手順: To a solution of 3-bromo-5-ethoxypyridine (53 g, 262 mmol) in DCM (200 mL) at 0° C. was slowly added m-CPBA (67.9 g, 393 mmol) over 30 min. After the resulting solution was stirred for 15 h, the mixture was washed with NaS2O3 solution and extracted with DCM (2×300 mL), dried over Na2SO4 and the organic phase was concentrated to give 3-bromo-5-ethoxypyridine 1-oxide (40 g, 165 mmol, 62.9% yield): 1H NMR (400 MHz, CD3OD) δ 8.19-8.18 (m, 1H), 8.08-8.07 (m, 1H), 7.50-7.49 (m, 1H), 4.17-4.15 (d, J=8.8 Hz, 2H), 1.43 (t, J=7.0 Hz, 3H); ES-LCMS m/z 217 (M+H). at 0° C. over 30 min the mixture was washed with NaS2O3 solution extracted with DCM (2×300 mL) dried over Na2SO4 the organic phase was concentrated

反応条件: temp:45.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 3-bromo-5-ethoxypyridine-1-oxide (40 g, 183 mmol) in DCM (200 mL) at 0° C. was slowly added POCl3 (159 mL, 1701 mmol) over 30 min. Then the resulting solution was warmed to 45° C. and stirred for 15 h. The mixture was concentrated and adjusted pH=9-10 with 10% NaOH solution, extracted with DCM (300 mL×2), dried over Na2SO4, filtered, and concentrated to give the crude product which was purified by silica column chromatography (10% EA: 90% PE, 800 g silica column). All fractions found to contain product by TLC (EA: PE=1:5, Rf=0.6) were combined and concentrated to yield an oil of 5-bromo-2-chloro-3-ethoxypyridine (30 g, 60.9 mmol, 33% yield): 1H NMR (400 MHz, CD3OD) δ 8.00-7.99 (d, J=2.0 Hz, 1H), 7.65-7.64 (d, J=2.0 Hz, 1H), 4.17-4.12 (m, 2H), 1.44 (t, J=7.0 Hz, 2H); ES-LCMS m/z 235 (M+H). at 0° C. over 30 min The mixture was concentrated adjusted pH=9-10 with 10% NaOH solution, extracted with DCM (300 mL×2) dried over Na2SO4 filtered concentrated to give the crude product which was purified by silica column chromatography (10% EA: 90% PE, 800 g silica column) concentrated