2-(2,4-dichlorophenoxy)benzonitrile

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: At 0° C., a 1.2 M solution of diisobutylaluminum hydride in toluene (12.3 ml, 14.8 mmol) was added dropwise to a solution of 2-(2,4-dichlorophenoxy)benzonitrile (3.0 g, 11.3 mmol) in THF (30 ml). The reaction mixture was warmed to room temperature and stirred for 16 hours. It was cooled to 0° C. Water (10 ml) was added dropwise. It was warmed to room temperature. The solid was removed by filtration through a plug of celite. The solvent was removed from the filtrate in vacuo. The crude product was purified by flash chromatography on silica (130 g), using ethyl acetate/heptane 1:3 as eluent, to give 800 mg of 2-(2,4-dichlorophenoxy)benzaldehyde. It was cooled to 0° C It was warmed to room temperature The solid was removed by filtration through a plug of celite The solvent was removed from the filtrate in vacuo The crude product was purified by flash chromatography on silica (130 g)

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: At 0° C., a 1.2 M solution of diisobutylaluminum hydride in toluene (12.3 ml, 14.8 mmol) was added dropwise to a solution of 2-(2,4-dichlorophenoxy)benzonitrile (3.0 g, 11.3 mmol) in THF (30 ml). The reaction mixture was warmed to room temperature and stirred for 16 hours. It was cooled to 0° C. Water (10 ml) was added dropwise. It was warmed to room temperature. The solid was removed by filtration through a plug of celite. The solvent was removed from the filtrate in vacuo. The crude product was purified by flash chromatography on silica (130 g), using ethyl acetate/heptane 1:3 as eluent, to give 800 mg of 2-(2,4-dichlorophenoxy)benzaldehyde. It was cooled to 0° C It was warmed to room temperature The solid was removed by filtration through a plug of celite The solvent was removed from the filtrate in vacuo The crude product was purified by flash chromatography on silica (130 g)

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

実験手順: At 0° C., a 1.2 M solution of diisobutylaluminum hydride in toluene (12.3 ml, 14.8 mmol) was added dropwise to a solution of 2-(2,4-dichlorophenoxy)benzonitrile (3.0 g, 11.3 mmol) in THF (30 ml). The reaction mixture was warmed to room temperature and stirred for 16 hours. It was cooled to 0° C. Water (10 ml) was added dropwise. It was warmed to room temperature. The solid was removed by filtration through a plug of celite. The solvent was removed from the filtrate in vacuo. The crude product was purified by flash chromatography on silica (130 g), using ethyl acetate/heptane 1:3 as eluent, to give 800 mg of 2-(2,4-dichlorophenoxy)benzaldehyde. It was cooled to 0° C It was warmed to room temperature The solid was removed by filtration through a plug of celite The solvent was removed from the filtrate in vacuo The crude product was purified by flash chromatography on silica (130 g)

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: AMR01057 A solution of 2-(2,4-dichlorophenoxy)benzonitrile (AMR01045, 1.39 g, 5.26 mmol) and KOH (1.77 g, 31.58 mmol) in EtOH (10 mL) and H2O (10 mL) was heated at reflux for 20 h. After adding water (20 mL) the solution was washed with DCM (3×10 mL). The aqueous was acidified with HCl 1M and a white solid precipitated. It was filtered, washed with water and dried. Flash chromatography on silica gel using DCM to DCM/MeOH 9:1 gradient as eluent gave 2-(2,4-dichlorophenoxy)benzoic acid (1.1 g, 74%) as a white solid, mp 161-163° C. (Lit. 159-162° C.) Rf: 0.36 (DCM/MeOH 9:1). 1H NMR (300 MHz, CDCl3) δ 6.79 (1H, dd, J=8.3, 0.8 Hz, ArH), 7.00 (1H, d, J=8.7 Hz, ArH), 7.23-7.28 (2H, m, ArH), 7.51 (1H, m, ArH), 7.52 (1H, d, J=7.5 Hz, ArH), 8.17 (1H, dd, J=7.8, 1.7 Hz, ArH), and 10.76 (1H, br s, COOH). at reflux for 20 h was washed with DCM (3×10 mL) a white solid precipitated It was filtered washed with water dried

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

実験手順: AMR01045 A mixture of 2,4-dichlorophenol (2.00 g, 12.27 mmol), 2-fluorobenzonitrile (1.49 g, 12.27 mmol) and potassium carbonate (1.7 g, 12.27 mmol) in DMF (10 mL) was stirred under reflux for 1.5 h. After removal of DMF, the residue was dissolved in DCM and washed with NaOH (5%, 3×20 mL) and brine. The organic layer was dried (MgSO4), filtered and evaporated and 2-(2,4-dichlorophenoxy)benzonitrile was obtained as an oil (2.73 g, 84%), which was used in the next step without further purification. Rf: 0.64 (DCM) 1H NMR (300 MHz, CDCl3) δ 6.73 (1H, dd, J=8.4 Hz), 7.13 (1H, d, J=8.7 Hz), 7.22 (1H, td, J=8.7, 1.0 Hz), 7.35 (1H, dd, J=8.7, 2.4 Hz), 7.56 (1H, d, J=2.4 Hz) and 7.73 (1H, dd, J=7.5, 2.7 Hz). under reflux for 1.5 h After removal of DMF the residue was dissolved in DCM washed with NaOH (5%, 3×20 mL) and brine The organic layer was dried (MgSO4) filtered evaporated

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

実験手順: At 0° C., a 1.2 M solution of diisobutylaluminum hydride in toluene (12.3 ml, 14.8 mmol) was added dropwise to a solution of 2-(2,4-dichlorophenoxy)benzonitrile (3.0 g, 11.3 mmol) in THF (30 ml). The reaction mixture was warmed to room temperature and stirred for 16 hours. It was cooled to 0° C. Water (10 ml) was added dropwise. It was warmed to room temperature. The solid was removed by filtration through a plug of celite. The solvent was removed from the filtrate in vacuo. The crude product was purified by flash chromatography on silica (130 g), using ethyl acetate/heptane 1:3 as eluent, to give 800 mg of 2-(2,4-dichlorophenoxy)benzaldehyde. It was cooled to 0° C It was warmed to room temperature The solid was removed by filtration through a plug of celite The solvent was removed from the filtrate in vacuo The crude product was purified by flash chromatography on silica (130 g)