2-[4-bromo-2-(trifluoromethyl)phenyl]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:

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

実験手順: A solution of (4-bromo-2-trifluoromethylphenyl)acetonitrile (2.28 g) in tetrahydrofuran (6 mL) was added to a suspension of sodium hydride (containing 60% in mineral oil, 362 mg) in tetrahydrofuran (12 mL) under ice-cooling. The mixture was stirred at the same temperature for 20 minutes. 1-Chloro-3-iodopropane (0.94 mL) was added dropwise to the reaction solution, and then the reaction solution was stirred at room temperature for 40 minutes. Ice water and heptane were added to the reaction solution, and the organic layer was separated. The resulting organic layer was washed with brine, dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (carrier: Wakogel™ C-200; elution solvent:heptane:ethyl acetate=49:1→19:1) to obtain 2.67 g of the title compound. The property values of the compound are as follows. cooling the reaction solution was stirred at room temperature for 40 minutes the organic layer was separated The resulting organic layer was washed with brine dried over anhydrous magnesium sulfate concentrated under reduced pressure The resulting residue was purified by silica gel column chromatography (carrier: Wakogel™ C-200; elution solvent:heptane:ethyl acetate=49:1→19:1)

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

実験手順: Potassium cyanide (630 mg) was added to an emulsion of 4-bromo-1-bromomethyl-2-trifluoromethylbenzene (3.86 g) in ethanol (15 mL)-water (5 mL), and the mixture was stirred at 70° C. for three hours and 15 minutes. Water and ethyl acetate were added to the reaction solution, and the organic layer was separated. The resulting organic layer was washed with brine, dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (carrier: Wakogel C-200; elution solvent:heptane:ethyl acetate=9:1) to obtain 2.28 g of the title compound. The property values of the compound are as follows. the organic layer was separated The resulting organic layer was washed with brine dried over anhydrous magnesium sulfate concentrated under reduced pressure The resulting residue was purified by silica gel column chromatography (carrier: Wakogel C-200; elution solvent:heptane:ethyl acetate=9:1)

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: o a stirred solution of (4-bromo-2-trifluoromethyl-phenyl)-acetonitrile (3.33 g, 12.61 mmol) from step 2 of example A(141), benzyltriethylammoniym chloride (0.057 g, 0.25 mmol) and 1-bromo-2-chloroethane (1.57 g, 10.94 mmol), was added dropwise a solution of NaOH 40% ( 3 mL). The reaction mixture was stirred 6 hours at 50° C. After this time the reaction was quenched with 1 N HCl (30 mL) and extracted with EtOAC (3×30 mL). The organic phase was dried over Na2SO4 and evaporated. The crude organic product was purified by flash column chromatography (10% EtOAc in hexanes) to give the product (3.1 g, 86%) as a clear oil. 1H NMR (400 MHz, CDCl3) δ 1.4–1.44 (m, 2H), 1.76–1.80 (m, 2H), 7.44 (d, J=8.3 Hz, 1 H), 7.69 (dd, J=8.3, 2 Hz, 1 H), 7.84 (d, J=2 Hz, 1 H). After this time the reaction was quenched with 1 N HCl (30 mL) extracted with EtOAC (3×30 mL) The organic phase was dried over Na2SO4 evaporated The crude organic product was purified by flash column chromatography (10% EtOAc in hexanes)

反応条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: o a stirred solution of (4-bromo-2-trifluoromethyl-phenyl)-acetonitrile (3.33 g, 12.61 mmol) from step 2 of example A(141), benzyltriethylammoniym chloride (0.057 g, 0.25 mmol) and 1-bromo-2-chloroethane (1.57 g, 10.94 mmol), was added dropwise a solution of NaOH 40% ( 3 mL). The reaction mixture was stirred 6 hours at 50° C. After this time the reaction was quenched with 1 N HCl (30 mL) and extracted with EtOAC (3×30 mL). The organic phase was dried over Na2SO4 and evaporated. The crude organic product was purified by flash column chromatography (10% EtOAc in hexanes) to give the product (3.1 g, 86%) as a clear oil. 1H NMR (400 MHz, CDCl3) δ 1.4–1.44 (m, 2H), 1.76–1.80 (m, 2H), 7.44 (d, J=8.3 Hz, 1 H), 7.69 (dd, J=8.3, 2 Hz, 1 H), 7.84 (d, J=2 Hz, 1 H). After this time the reaction was quenched with 1 N HCl (30 mL) extracted with EtOAC (3×30 mL) The organic phase was dried over Na2SO4 evaporated The crude organic product was purified by flash column chromatography (10% EtOAc in hexanes)

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

実験手順: NaH 95% (2.28 g, 94.7 mmol) was suspended in DMF (25mL) and cooled to 0° C. (4-Bromo-2-trifluoromethyl-phenyl)-acetonitrile (5 g, 18.94 mmol) from step 2 above, was dissolved in THF (35 mL) and slowly added via cannula to the NaH suspension. The reaction mixture was stirred for 20 min. Methyl iodide (11.79 mL, 189.36 mmol) was added and the resulting mixture was stirred overnight at room temperature. Reaction was quenched with H2O (100 mL). Solvents were removed in vacuo and residue partitioned between EtOAc and 1 N HCl (100 mL). The organic phase was dried over Na2SO4 and evaporated. The crude organic product was purified by flash column chromatography (5% EtOAc in hexanes) to give the product (4.14 g, 75%) as a clear oil. 1H NMR (400 MHz, CDCl3) δ 1.6 (s, 6H), 7.46 (d, J=5.3 Hz, 1 H), 7.67 (d, J=8.3 Hz, 1 H), 7.78 (s, 1H). the resulting mixture was stirred overnight at room temperature Reaction was quenched with H2O (100 mL) Solvents were removed in vacuo and residue partitioned between EtOAc and 1 N HCl (100 mL) The organic phase was dried over Na2SO4 evaporated The crude organic product was purified by flash column chromatography (5% EtOAc in hexanes)

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

実験手順: A mixture of 4-methyl-3-trifluorobromobenzene (33.26 g, 104.261 mmol) from step 1 above, KCN (20.43 g, 313.67 mmol) and tetrabutylammonium bromide (3.37 g, 10.45 mmol) in CH2Cl2/H2O 1:1 (300 mL) was stirred at room temperature for 4 hours. The layers were separated and the organic layer washed with H2O (100 mL) 1N HCl (100 mL), brine, dried over Na2SO4 and then concentrated to a brown oil which was purified by flash column chromatography (0% to 20% EtOAc in hexanes) to give the product as a clear oil (14.9 g, 54%). 1H NMR (400 MHz, CDCl3) δ 3.91 (s, 2H), 7.57 (d, J=8.3 Hz, 1 H), 7.75 (dd, J=8.3, 2 Hz, 1 H), 7.84 (d, J=2 Hz, 1 H). The layers were separated the organic layer washed with H2O (100 mL) 1N HCl (100 mL), brine dried over Na2SO4 concentrated to a brown oil which was purified by flash column chromatography (0% to 20% EtOAc in hexanes)

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

実験手順: A mixture of 4-methyl-3-trifluorobromobenzene (33.26 g, 104.261 mmol) from step 1 above, KCN (20.43 g, 313.67 mmol) and tetrabutylammonium bromide (3.37 g, 10.45 mmol) in CH2Cl2/H2O 1:1 (300 mL) was stirred at room temperature for 4 hours. The layers were separated and the organic layer washed with H2O (100 mL) 1N HCl (100 mL), brine, dried over Na2SO4 and then concentrated to a brown oil which was purified by flash column chromatography (0% to 20% EtOAc in hexanes) to give the product as a clear oil (14.9 g, 54%). 1H NMR (400 MHz, CDCl3) δ 3.91 (s, 2H), 7.57 (d, J=8.3 Hz, 1 H), 7.75 (dd, J=8.3, 2 Hz, 1 H), 7.84 (d, J=2 Hz, 1 H). The layers were separated the organic layer washed with H2O (100 mL) 1N HCl (100 mL), brine dried over Na2SO4 concentrated to a brown oil which was purified by flash column chromatography (0% to 20% EtOAc in hexanes)

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

実験手順: A solution of (4-bromo-2-trifluoromethylphenyl)acetonitrile (2.28 g) in tetrahydrofuran (6 mL) was added to a suspension of sodium hydride (containing 60% in mineral oil, 362 mg) in tetrahydrofuran (12 mL) under ice-cooling. The mixture was stirred at the same temperature for 20 minutes. 1-Chloro-3-iodopropane (0.94 mL) was added dropwise to the reaction solution, and then the reaction solution was stirred at room temperature for 40 minutes. Ice water and heptane were added to the reaction solution, and the organic layer was separated. The resulting organic layer was washed with brine, dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (carrier: Wakogel™ C-200; elution solvent:heptane:ethyl acetate=49:1→19:1) to obtain 2.67 g of the title compound. The property values of the compound are as follows. cooling the reaction solution was stirred at room temperature for 40 minutes the organic layer was separated The resulting organic layer was washed with brine dried over anhydrous magnesium sulfate concentrated under reduced pressure The resulting residue was purified by silica gel column chromatography (carrier: Wakogel™ C-200; elution solvent:heptane:ethyl acetate=49:1→19:1)