3-chloro-4,5-difluoroaniline

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 3-chloro-4,5-difluoroaniline (2.1 g, 12.96 mmol) in hydrobromic acid (40% in H2O, 18.7 mL) was added dropwise a solution of sodium nitrite (0.96 g, 13.6 mol) in 7.5 mL H2O at 0° C. Then the mixture was poured into a solution of copper(I) bromide (3.5 g, 23.7 mmol) in hydrobromic acid (40% in H2O, 15 mL) at 0° C. The cooling bath was then removed and the mixture was heated at 60° C. overnight. After cooling, the mixture was basified with a solution 2N NaOH solution to pH=9 and diluted with CH2Cl2. After separation, the combined organic layers were washed with brine, dried over Na2SO4 and then concentrated to get crude product, which was purified by column with PE/EtOAc (from 100:1 to 20:1) as eluant to afford 2 g product. Yield 68.3%; 1H NMR (400 MHz, CDCl3): δ 7.37-7.35 (m, 1 H), 7.30-7.25 (m, 1 H) ppm. The cooling bath was then removed After cooling diluted with CH2Cl2 After separation the combined organic layers were washed with brine dried over Na2SO4 concentrated to get crude product, which was purified by column with PE/EtOAc (from 100:1 to 20:1) as eluant

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 3-chloro-4,5-difluoroaniline (2.1 g, 12.96 mmol) in hydrobromic acid (40% in H2O, 18.7 mL) was added dropwise a solution of sodium nitrite (0.96 g, 13.6 mol) in 7.5 mL H2O at 0° C. Then the mixture was poured into a solution of copper(I) bromide (3.5 g, 23.7 mmol) in hydrobromic acid (40% in H2O, 15 mL) at 0° C. The cooling bath was then removed and the mixture was heated at 60° C. overnight. After cooling, the mixture was basified with a solution 2N NaOH solution to pH=9 and diluted with CH2Cl2. After separation, the combined organic layers were washed with brine, dried over Na2SO4 and then concentrated to get crude product, which was purified by column with PE/EtOAc (from 100:1 to 20:1) as eluant to afford 2 g product. Yield 68.3%; 1H NMR (400 MHz, CDCl3): δ 7.37-7.35 (m, 1 H), 7.30-7.25 (m, 1 H) ppm. The cooling bath was then removed After cooling diluted with CH2Cl2 After separation the combined organic layers were washed with brine dried over Na2SO4 concentrated to get crude product, which was purified by column with PE/EtOAc (from 100:1 to 20:1) as eluant

反応条件: temp:62.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 1-Chloro-2,3-difluoro-5-nitrobenzene (3 g, 15.6 mmol) was added to acetic acid (10 mL) and methanol (250 mL). To this mixture was added iron powder (3.0 g) in portions, stirred for 2 h at 60-65° C., cooled to room temperature, and filtered. The filterate was stripped to a brown solid, which was extracted with ethyl acetate (3×200 mL), washed with 1N NaOH (3×100 mL), and brine (2×100 mL). The organic layer was dried over anhydrous magnesium sulfate, filtered and stripped down to yield the product as a pale yellow solid (2.6 g). Yield 100%; 1H NMR (400 MHz, CDCl3): δ 6.41 (m, 2 H), 3.65 (br s, 2 H) ppm. cooled to room temperature filtered was extracted with ethyl acetate (3×200 mL) washed with 1N NaOH (3×100 mL), and brine (2×100 mL) The organic layer was dried over anhydrous magnesium sulfate filtered

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 3-chloro-4,5-difluoroaniline (2.1 g, 12.96 mmol) in hydrobromic acid (40% in H2O, 18.7 mL) was added dropwise a solution of sodium nitrite (0.96 g, 13.6 mol) in 7.5 mL H2O at 0° C. Then the mixture was poured into a solution of copper(I) bromide (3.5 g, 23.7 mmol) in hydrobromic acid (40% in H2O, 15 mL) at 0° C. The cooling bath was then removed and the mixture was heated at 60° C. overnight. After cooling, the mixture was basified with a solution 2N NaOH solution to pH=9 and diluted with CH2Cl2. After separation, the combined organic layers were washed with brine, dried over Na2SO4 and then concentrated to get crude product, which was purified by column with PE/EtOAc (from 100:1 to 20:1) as eluant to afford 2 g product. Yield 68.3%; 1H NMR (400 MHz, CDCl3): δ 7.37-7.35 (m, 1 H), 7.30-7.25 (m, 1 H) ppm. The cooling bath was then removed After cooling diluted with CH2Cl2 After separation the combined organic layers were washed with brine dried over Na2SO4 concentrated to get crude product, which was purified by column with PE/EtOAc (from 100:1 to 20:1) as eluant

反応条件: temp:62.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 1-Chloro-2,3-difluoro-5-nitrobenzene (3 g, 15.6 mmol) was added to acetic acid (10 mL) and methanol (250 mL). To this mixture was added iron powder (3.0 g) in portions, stirred for 2 h at 60-65° C., cooled to room temperature, and filtered. The filterate was stripped to a brown solid, which was extracted with ethyl acetate (3×200 mL), washed with 1N NaOH (3×100 mL), and brine (2×100 mL). The organic layer was dried over anhydrous magnesium sulfate, filtered and stripped down to yield the product as a pale yellow solid (2.6 g). Yield 100%; 1H NMR (400 MHz, CDCl3): δ 6.41 (m, 2 H), 3.65 (br s, 2 H) ppm. cooled to room temperature filtered was extracted with ethyl acetate (3×200 mL) washed with 1N NaOH (3×100 mL), and brine (2×100 mL) The organic layer was dried over anhydrous magnesium sulfate filtered

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 3-chloro-4,5-difluoroaniline (2.1 g, 12.96 mmol) in hydrobromic acid (40% in H2O, 18.7 mL) was added dropwise a solution of sodium nitrite (0.96 g, 13.6 mol) in 7.5 mL H2O at 0° C. Then the mixture was poured into a solution of copper(I) bromide (3.5 g, 23.7 mmol) in hydrobromic acid (40% in H2O, 15 mL) at 0° C. The cooling bath was then removed and the mixture was heated at 60° C. overnight. After cooling, the mixture was basified with a solution 2N NaOH solution to pH=9 and diluted with CH2Cl2. After separation, the combined organic layers were washed with brine, dried over Na2SO4 and then concentrated to get crude product, which was purified by column with PE/EtOAc (from 100:1 to 20:1) as eluant to afford 2 g product. Yield 68.3%; 1H NMR (400 MHz, CDCl3): δ 7.37-7.35 (m, 1 H), 7.30-7.25 (m, 1 H) ppm. The cooling bath was then removed After cooling diluted with CH2Cl2 After separation the combined organic layers were washed with brine dried over Na2SO4 concentrated to get crude product, which was purified by column with PE/EtOAc (from 100:1 to 20:1) as eluant

反応条件: temp:62.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 1-Chloro-2,3-difluoro-5-nitrobenzene (3 g, 15.6 mmol) was added to acetic acid (10 mL) and methanol (250 mL). To this mixture was added iron powder (3.0 g) in portions, stirred for 2 h at 60-65° C., cooled to room temperature, and filtered. The filterate was stripped to a brown solid, which was extracted with ethyl acetate (3×200 mL), washed with 1N NaOH (3×100 mL), and brine (2×100 mL). The organic layer was dried over anhydrous magnesium sulfate, filtered and stripped down to yield the product as a pale yellow solid (2.6 g). Yield 100%; 1H NMR (400 MHz, CDCl3): δ 6.41 (m, 2 H), 3.65 (br s, 2 H) ppm. cooled to room temperature filtered was extracted with ethyl acetate (3×200 mL) washed with 1N NaOH (3×100 mL), and brine (2×100 mL) The organic layer was dried over anhydrous magnesium sulfate filtered