2-(2,6-difluorophenyl)acetonitrile

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

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

実験手順: To a stirred mixture 2,6-difluorophenylacetonitrile (3.06 g, 20.0 mmol) in 30 mL of H2SO4 at 0° C. was added 12 mL of a 1:1 mixture of nitric acid and sulfuric acid. The reaction mixture stirred for 5 h and poured onto crushed ice. The resulting solid was filtered and air dried to give 2,6-difluoro-3-nitro-phenylacetamide. poured onto crushed ice The resulting solid was filtered air dried

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

実験手順: To a solution of (2,6-difluorophenyl)acetonitrile (5 g, 32.7 mmol) in conc. Sulphuric acid (15 mL) at −78° C. was added dropwise a solution of nitric acid (65%, 2.25 mL, 32.7 mmol) in conc. sulphuric acid (5 mL). On completion of addition the reaction mixture was poured onto ice and the precipitate that formed collected by filtration, washed with water and dried in vacuo to give the title product as a white solid (6.4 g, 100%). 1H NMR 400 MHz δ (CDCl3): 8.24-8.16 (1H, m), 7.17 (1H, ddd, J=9.6, 7.8, 1.9 Hz), 3.84 (2H, t, J=1.2 Hz). On completion of addition the reaction mixture was poured onto ice the precipitate that formed collected by filtration washed with water dried in vacuo

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

実験手順: To a solution of (2,6-difluorophenyl)acetonitrile (5 g, 32.7 mmol) in conc. Sulphuric acid (15 mL) at −78° C. was added dropwise a solution of nitric acid (65%, 2.25 mL, 32.7 mmol) in conc. sulphuric acid (5 mL). On completion of addition the reaction mixture was poured onto ice and the precipitate that formed collected by filtration, washed with water and dried in vacuo to give the title product as a white solid (6.4 g, 100%). 1H NMR 400 MHz δ (CDCl3): 8.24-8.16 (1H, m), 7.17 (1H, ddd, J=9.6, 7.8, 1.9 Hz), 3.84 (2H, t, J=1.2 Hz). On completion of addition the reaction mixture was poured onto ice the precipitate that formed collected by filtration washed with water dried in vacuo

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

実験手順: 2,6-Difluorophenylacetonitrile (15.8 g, 100 mmol) was dissolved in tetrahydrofuran (75 mL) at room temperature. The solution was cooled in an ice bath and borane.THF complex (100mL, 100 mmol) was added dropwise over 15 minutes under nitrogen atmosphere. The ice bath was removed after borane addition was complete and the mixture was stirred at room temperature for 23 hours under nitrogen atmosphere. Saturated aqueous ammonium chloride solution (20 mL) was added dropwise with stirring over 30 minutes. The reaction mixture was filtered through diatomaceous earth, concentrated to an oil, redissolved in ethyl acetate/water, and adjusted to pH 1.0 with concentrated hydrochloric acid. The mixture was filtered through diatomaceous earth and the ethyl acetate layer extracted with 1N hydrochloric acid (4×10 mL). The combined acidic aqueous extracts were washed with ethyl acetate (2×50 ml). Solid sodium chloride was added to the acidic aqueous extracts, adjusted to pH 9.0 with solid sodium bicarbonate and 5N sodium hydroxide solution, and the mixture extracted with methylene chloride (7×50 mL). The combined methylene chloride extracts were washed with brine solution, dried over anhydrous sodium sulfate, filtered, and concentrated to yield 10.6 g (68%) of the titled product as a nearly colorless oil: The solution was cooled in an ice bath THF complex (100mL, 100 mmol) was added dropwise over 15 minutes under nitrogen atmosphere The ice bath was removed after borane addition Saturated aqueous ammonium chloride solution (20 mL) was added dropwise with stirring over 30 minutes The reaction mixture was filtered through diatomaceous earth concentrated to an oil redissolved in ethyl acetate/water The mixture was filtered through diatomaceous earth the ethyl acetate layer extracted with 1N hydrochloric acid (4×10 mL) The combined acidic aqueous extracts were washed with ethyl acetate (2×50 ml) Solid sodium chloride was added to the acidic aqueous extracts the mixture extracted with methylene chloride (7×50 mL) The combined methylene chloride extracts were washed with brine solution dried over anhydrous sodium sulfate filtered concentrated

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

実験手順: 2-(2,6-Difluorophenyl)acetonitrile (2.34 g, 15.28 mmol) was added to potassium boron hydride (3.29 g, 61.12 mmol) and Raney nickel (0.897 g, 15.28 mmol) in 50 mL of absolute ethanol while stirring. Then, vigorously stirring was continued at room temperature for 5 hrs. Then, vigorously stirring

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

実験手順: 2-(2,6-Difluorophenyl)acetonitrile (2.34 g, 15.28 mmol) was added to potassium boron hydride (3.29 g, 61.12 mmol) and Raney nickel (0.897 g, 15.28 mmol) in 50 mL of absolute ethanol while stirring. Then, vigorously stirring was continued at room temperature for 5 hrs. Then, vigorously stirring

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

実験手順: 2,6-Difluorophenylacetonitrile (15.8 g, 100 mmol) was dissolved in tetrahydrofuran (75 mL) at room temperature. The solution was cooled in an ice bath and borane THF complex (100mL, 100 mmol) was added dropwise over 15 minutes under nitrogen atmosphere. The ice bath was removed after borane addition was complete and the mixture was stirred at room temperature for 23 hours under nitrogen atmosphere. Saturated aqueous ammonium chloride solution (20 mL) was added dropwise with stirring over 30 minutes. The reaction mixture was filtered through diatomaceous earth, concentrated to an oil, redissolved in ethyl acetate/water, and adjusted to pH 1.0 with concentrated hydrochloric acid. The mixture was filtered through diatomaceous earch and the ethyl acetate layer extracted with 1N hydrochloric acid (4×10 mL). The combined acidic aqueous extracts were washed with ethyl acetate (2×50 ml). Solid sodium chloride was added to the acidic aqueous extracts, adjusted to pH 9.0 with solid sodium bicarbonate and 5N sodium hydroxide solution, and the mixture extracted with methylene chloride (7×50 mL). The combined methylene chloride extracts were washed with brine solution, dried over anhydrous sodium sulfate, filtered, and concentrated to yield 10.6 g (68%) of the titled product as a nearly colorless oil: The solution was cooled in an ice bath borane THF complex (100mL, 100 mmol) was added dropwise over 15 minutes under nitrogen atmosphere The ice bath was removed after borane addition Saturated aqueous ammonium chloride solution (20 mL) was added dropwise with stirring over 30 minutes The reaction mixture was filtered through diatomaceous earth concentrated to an oil redissolved in ethyl acetate/water The mixture was filtered through diatomaceous earch the ethyl acetate layer extracted with 1N hydrochloric acid (4×10 mL) The combined acidic aqueous extracts were washed with ethyl acetate (2×50 ml) Solid sodium chloride was added to the acidic aqueous extracts the mixture extracted with methylene chloride (7×50 mL) The combined methylene chloride extracts were washed with brine solution dried over anhydrous sodium sulfate filtered concentrated

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 5.0 g (32.65 mmole) of 2,6-difluorophenylacetonitrile in 25 ml of anhydrous tetrahydrofuran at room temperature under nitrogen was added 33.0 ml (33.0 mmole) of 1.0 molar boranetetrahydrofuran complex by syringe. The mixture was stirred 4 hours, cooled in an ice bath, and quenched under nitrogen with a solution of 10.7 ml of concentrated hydrochloric acid in 22 ml of water. The mixture was heated to re flux, stirred I hr., and the tetrahydrofuran was removed by downward distillation. The milky white suspension was diluted with 22 ml of toluene and stirred 5 minutes longer. The layers were separated and the aqueous was extracted with 20 ml of hot toluene. The aqueous layer was cooled to 0° C., 50 ml of methylene chloride and 10 ml of 50% sodium hydroxide was added, and the layers were separated. The aqueous layer was extracted with methylene chloride (2×) and the combined organics were dried over sodium sulfate. Concentration gave 2.8 g (55%) of 2,6difluorophenethylamine as a light yellow liquid; 1H NMR (300 MHz, CDCl3) δ 7.10-7.30 (m, 1H), 6.80-7.00 (t, 2H), 2.80-3.00 (m, 2H), 2.70-2.80 (m, 2H), 1.35 (s, 2H) cooled in an ice bath quenched under nitrogen with a solution of 10.7 ml of concentrated hydrochloric acid in 22 ml of water The mixture was heated stirred I hr , and the tetrahydrofuran was removed by downward distillation The milky white suspension was diluted with 22 ml of toluene stirred 5 minutes longer The layers were separated the aqueous was extracted with 20 ml of hot toluene 50 ml of methylene chloride and 10 ml of 50% sodium hydroxide was added the layers were separated The aqueous layer was extracted with methylene chloride (2×) the combined organics were dried over sodium sulfate Concentration

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

実験手順: To a stirred mixture 2,6-difluorophenylacetonitrile (3.06 g, 20.0 mmol) in 30 mL of H2SO4 at 0° C. was added 12 mL of a 1:1 mixture of nitric acid and sulfuric acid. The reaction mixture stirred for 5 h and poured onto crushed ice. The resulting solid was filtered and air dried to give 2,6-difluoro-3-nitro-phenylacetamide. poured onto crushed ice The resulting solid was filtered air dried

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

実験手順: To a stirred mixture 2,6-difluorophenylacetonitrile (3.06 g, 20.0 mmol) in 30 mL of H2SO4 at 0° C. was added 12 mL of a 1:1 mixture of nitric acid and sulfuric acid. The reaction mixture stirred for 5 h and poured onto crushed ice. The resulting solid was filtered and air dried to give 2,6-difluoro-3-nitro-phenylacetamide. poured onto crushed ice The resulting solid was filtered air dried