2-(2-fluoro-3-methoxyphenyl)acetonitrile

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

実験手順: 24.89 g (142.56 mmol) of 2-fluoro-3-methoxybenzyl chloride is stirred in 200 ml of DMSO with 8.38 g (171.07 mmol) of sodium cyanide for three hours at 90° C. The reaction mixture is poured into water and extracted four times with methyl tert-butyl ether. The combined organic phases are washed with brine, dried, the desiccant is suctioned off, and the solvent is spun off. First, only a portion of the residue (21.43 g) is incorporated in crude form into the next stage. extracted four times with methyl tert-butyl ether The combined organic phases are washed with brine dried

反応条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 1-(chloromethyl)-2-fluoro-3-methoxybenzene (8.6 g, 49.3 mmol) in ethanol (60 mL) and water (10 mL), sodium cyanide (4.8 g, 98.5 mmol) was added. The resulting solution was heated at 70° C. for 16 h. After cooling to room temperature, the solution was poured into water (200 mL) and extracted with ethyl acetate (2×200 mL). The combined organic layers were washed (brine), dried (Na2SO4), and concentrated in vacuo to give the title compound (6.7 g). 1H NMR (CDCl3): δ 7.13-7.07 (m, 1H), 7.02-6.92 (m, 2H), 3.89 (s, 3H), 3.81 (s, 2H). After cooling to room temperature extracted with ethyl acetate (2×200 mL) The combined organic layers were washed (brine) dried (Na2SO4) concentrated in vacuo

反応条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 1-(chloromethyl)-2-fluoro-3-methoxybenzene (8.6 g, 49.3 mmol) in ethanol (60 mL) and water (10 mL), sodium cyanide (4.8 g, 98.5 mmol) was added. The resulting solution was heated at 70° C. for 16 h. After cooling to room temperature, the solution was poured into water (200 mL) and extracted with ethyl acetate (2×200 mL). The combined organic layers were washed (brine), dried (Na2SO4), and concentrated in vacuo to give the title compound (6.7 g). 1H NMR (CDCl3): δ 7.13-7.07 (m, 1H), 7.02-6.92 (m, 2H), 3.89 (s, 3H), 3.81 (s, 2H). After cooling to room temperature extracted with ethyl acetate (2×200 mL) The combined organic layers were washed (brine) dried (Na2SO4) concentrated in vacuo

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

実験手順: To a mixture of 2-(2-fluoro-3-methoxyphenyl)acetonitrile (6.7 g, 40.6 mmol) in water (40 mL) and methanol (40 mL), sodium hydroxide (3.2 g, 81.1 mmol) was added. The resulting mixture was stirred at 60° C. for 5 h. After cooling to room temperature, methanol was evaporated under reduced pressure. The residue was acidified with 10% HCl until pH 5. The resulting precipitate was collected by filtration and dried to afford the title compound (6.3 g). was added After cooling to room temperature methanol was evaporated under reduced pressure The resulting precipitate was collected by filtration dried

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

実験手順: 24.89 g (142.56 mmol) of 2-fluoro-3-methoxybenzyl chloride is stirred in 200 ml of DMSO with 8.38 g (171.07 mmol) of sodium cyanide for three hours at 90° C. The reaction mixture is poured into water and extracted four times with methyl tert-butyl ether. The combined organic phases are washed with brine, dried, the desiccant is suctioned off, and the solvent is spun off. First, only a portion of the residue (21.43 g) is incorporated in crude form into the next stage. extracted four times with methyl tert-butyl ether The combined organic phases are washed with brine dried

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

実験手順: 4 g (24.22 mmol) of 2-fluoro-3-methoxybenzyl cyanide is dissolved in 38 ml of N,N-dimethylformamide and mixed with 6.87 g (48.35 mmol) of methyl iodide. At 0° C., 2.11 g (48.35 mmol) of sodium hydride (55%) is added in portions within 45 minutes. After 20 hours of stirring at room temperature, the batch is poured into ice water and extracted three times with 200 ml each of diethyl ether. The organic phases are washed with water and brine and dried. After the desiccant is filtered off and after the solvent is spun off, the residue is chromatographed on silica gel (mobile solvent ethyl acetate/hexane). 4.66 g (99.5%) of the desired compound is isolated. extracted three times with 200 ml each of diethyl ether The organic phases are washed with water and brine dried After the desiccant is filtered off the residue is chromatographed on silica gel (mobile solvent ethyl acetate/hexane)

反応条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 1-(chloromethyl)-2-fluoro-3-methoxybenzene (8.6 g, 49.3 mmol) in ethanol (60 mL) and water (10 mL), sodium cyanide (4.8 g, 98.5 mmol) was added. The resulting solution was heated at 70° C. for 16 h. After cooling to room temperature, the solution was poured into water (200 mL) and extracted with ethyl acetate (2×200 mL). The combined organic layers were washed (brine), dried (Na2SO4), and concentrated in vacuo to give the title compound (6.7 g). 1H NMR (CDCl3): δ 7.13-7.07 (m, 1H), 7.02-6.92 (m, 2H), 3.89 (s, 3H), 3.81 (s, 2H). After cooling to room temperature extracted with ethyl acetate (2×200 mL) The combined organic layers were washed (brine) dried (Na2SO4) concentrated in vacuo

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

実験手順: To a mixture of 2-(2-fluoro-3-methoxyphenyl)acetonitrile (6.7 g, 40.6 mmol) in water (40 mL) and methanol (40 mL), sodium hydroxide (3.2 g, 81.1 mmol) was added. The resulting mixture was stirred at 60° C. for 5 h. After cooling to room temperature, methanol was evaporated under reduced pressure. The residue was acidified with 10% HCl until pH 5. The resulting precipitate was collected by filtration and dried to afford the title compound (6.3 g). was added After cooling to room temperature methanol was evaporated under reduced pressure The resulting precipitate was collected by filtration dried

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

実験手順: 24.89 g (142.56 mmol) of 2-fluoro-3-methoxybenzyl chloride is stirred in 200 ml of DMSO with 8.38 g (171.07 mmol) of sodium cyanide for three hours at 90° C. The reaction mixture is poured into water and extracted four times with methyl tert-butyl ether. The combined organic phases are washed with brine, dried, the desiccant is suctioned off, and the solvent is spun off. First, only a portion of the residue (21.43 g) is incorporated in crude form into the next stage. extracted four times with methyl tert-butyl ether The combined organic phases are washed with brine dried

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

実験手順: 4 g (24.22 mmol) of 2-fluoro-3-methoxybenzyl cyanide is dissolved in 38 ml of N,N-dimethylformamide and mixed with 6.87 g (48.35 mmol) of methyl iodide. At 0° C., 2.11 g (48.35 mmol) of sodium hydride (55%) is added in portions within 45 minutes. After 20 hours of stirring at room temperature, the batch is poured into ice water and extracted three times with 200 ml each of diethyl ether. The organic phases are washed with water and brine and dried. After the desiccant is filtered off and after the solvent is spun off, the residue is chromatographed on silica gel (mobile solvent ethyl acetate/hexane). 4.66 g (99.5%) of the desired compound is isolated. extracted three times with 200 ml each of diethyl ether The organic phases are washed with water and brine dried After the desiccant is filtered off the residue is chromatographed on silica gel (mobile solvent ethyl acetate/hexane)

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

実験手順: 4 g (24.22 mmol) of 2-fluoro-3-methoxybenzyl cyanide is dissolved in 38 ml of N,N-dimethylformamide and mixed with 6.87 g (48.35 mmol) of methyl iodide. At 0° C., 2.11 g (48.35 mmol) of sodium hydride (55%) is added in portions within 45 minutes. After 20 hours of stirring at room temperature, the batch is poured into ice water and extracted three times with 200 ml each of diethyl ether. The organic phases are washed with water and brine and dried. After the desiccant is filtered off and after the solvent is spun off, the residue is chromatographed on silica gel (mobile solvent:ethyl acetate/hexane). 4.66 g (99.5%) of the desired compound is isolated. extracted three times with 200 ml each of diethyl ether The organic phases are washed with water and brine dried After the desiccant is filtered off the residue is chromatographed on silica gel (mobile solvent:ethyl acetate/hexane)