2-[(2,3-dichlorophenyl)methyl]-4,4,4-trifluoro-3-oxobutanenitrile

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-(2,3-dichlorobenzyl)-4,4,4-trifluoro-3-oxobutanenitrile (10.0 g, 33.77 mmol) in ethanol (800 mL) was added hydrazine hydrate (1.86 g, 37.15 mmol) and the resulting solution was stirred under reflux for 16 h. The mixture was cooled to room temperature and concentrated. The residue was purified by silica gel column (petroleum ether/ethyl acetate=2/1) and reverse-phase Prep-HPLC to provide the titled compound (1.6 g, 15%) as a yellow oil; LC/MS: MS (ES+) m/e 310 (MH+); 1H NMR (300 MHz, DMSO-d6) δ ppm 3.85 (s, 2H), 6.78 (dd, J=1.2, 7.8 Hz, 1H), 7.25 (t, J=7.8 Hz, 1H), 7.47 (dd, J=1.2, 7.8 Hz, 1H). under reflux for 16 h concentrated The residue was purified by silica gel column (petroleum ether/ethyl acetate=2/1) and reverse-phase Prep-HPLC

反応条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a mixture of 3-(2,3-dichlorophenyl)propanenitrile (100 mg, 0.5 mmol) in THF (20 mL) was added LDA (0.5 mL, 2 N in hexane, 1 mmol) dropwise at −78° C. under nitrogen. The mixture was stirred at −78° C. for 0.5 h. Then ethyl 2,2,2-trifluoroacetate (177.5 mg, 1.25 mmol) was added to the mixture dropwise. This solution was stirred at −78° C. for 5 h and diluted with sat. aq. ammonium chloride solution and 1N hydrochloric acid. This solution was extracted with EA (30 mL*3). The combined organic layers were washed with water and brine, dried over sodium sulphate, concentrated under reduced pressure. The residue was purified by a silica gel chromatography to give the titled product (82 mg, 55%) as a yellow solid; LC/MS: MS (ES+) m/e 296 (MH+); 1H NMR (300 MHz, CDCl3) δ ppm 3.03 (dd, J=12.9, 14.1 Hz, 1H), 3.52-3.60 (m, 2H), 7.20-7.32 (m, 2H), 7.43-7.51 (m, 1H). This solution was stirred at −78° C. for 5 h This solution was extracted with EA (30 mL*3) The combined organic layers were washed with water and brine dried over sodium sulphate concentrated under reduced pressure The residue was purified by a silica gel chromatography

反応条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a mixture of 3-(2,3-dichlorophenyl)propanenitrile (100 mg, 0.5 mmol) in THF (20 mL) was added LDA (0.5 mL, 2 N in hexane, 1 mmol) dropwise at −78° C. under nitrogen. The mixture was stirred at −78° C. for 0.5 h. Then ethyl 2,2,2-trifluoroacetate (177.5 mg, 1.25 mmol) was added to the mixture dropwise. This solution was stirred at −78° C. for 5 h and diluted with sat. aq. ammonium chloride solution and 1N hydrochloric acid. This solution was extracted with EA (30 mL*3). The combined organic layers were washed with water and brine, dried over sodium sulphate, concentrated under reduced pressure. The residue was purified by a silica gel chromatography to give the titled product (82 mg, 55%) as a yellow solid; LC/MS: MS (ES+) m/e 296 (MH+); 1H NMR (300 MHz, CDCl3) δ ppm 3.03 (dd, J=12.9, 14.1 Hz, 1H), 3.52-3.60 (m, 2H), 7.20-7.32 (m, 2H), 7.43-7.51 (m, 1H). This solution was stirred at −78° C. for 5 h This solution was extracted with EA (30 mL*3) The combined organic layers were washed with water and brine dried over sodium sulphate concentrated under reduced pressure The residue was purified by a silica gel chromatography

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-(2,3-dichlorobenzyl)-4,4,4-trifluoro-3-oxobutanenitrile (10.0 g, 33.77 mmol) in ethanol (800 mL) was added hydrazine hydrate (1.86 g, 37.15 mmol) and the resulting solution was stirred under reflux for 16 h. The mixture was cooled to room temperature and concentrated. The residue was purified by silica gel column (petroleum ether/ethyl acetate=2/1) and reverse-phase Prep-HPLC to provide the titled compound (1.6 g, 15%) as a yellow oil; LC/MS: MS (ES+) m/e 310 (MH+); 1H NMR (300 MHz, DMSO-d6) δ ppm 3.85 (s, 2H), 6.78 (dd, J=1.2, 7.8 Hz, 1H), 7.25 (t, J=7.8 Hz, 1H), 7.47 (dd, J=1.2, 7.8 Hz, 1H). under reflux for 16 h concentrated The residue was purified by silica gel column (petroleum ether/ethyl acetate=2/1) and reverse-phase Prep-HPLC

反応条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a mixture of 3-(2,3-dichlorophenyl)propanenitrile (100 mg, 0.5 mmol) in THF (20 mL) was added LDA (0.5 mL, 2 N in hexane, 1 mmol) dropwise at −78° C. under nitrogen. The mixture was stirred at −78° C. for 0.5 h. Then ethyl 2,2,2-trifluoroacetate (177.5 mg, 1.25 mmol) was added to the mixture dropwise. This solution was stirred at −78° C. for 5 h and diluted with sat. aq. ammonium chloride solution and 1N hydrochloric acid. This solution was extracted with EA (30 mL*3). The combined organic layers were washed with water and brine, dried over sodium sulphate, concentrated under reduced pressure. The residue was purified by a silica gel chromatography to give the titled product (82 mg, 55%) as a yellow solid; LC/MS: MS (ES+) m/e 296 (MH+); 1H NMR (300 MHz, CDCl3) δ ppm 3.03 (dd, J=12.9, 14.1 Hz, 1H), 3.52-3.60 (m, 2H), 7.20-7.32 (m, 2H), 7.43-7.51 (m, 1H). This solution was stirred at −78° C. for 5 h This solution was extracted with EA (30 mL*3) The combined organic layers were washed with water and brine dried over sodium sulphate concentrated under reduced pressure The residue was purified by a silica gel chromatography