3-chloro-4,4,4-trifluoro-2-phenylbut-2-enal

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

実験手順: To a solution of ethyl 2-mercaptoacetate (0.88 g, 6.75 mmol) in THF (45 mL) NaH (271 mg, 6.75 mmol, 60% in mineral oil) is added at −10° C. The mixture is stirred at 0° C. for 30 min before a solution of 3-chloro-4,4,4-trifluoro-2-phenyl-but-2-enal 1.32 g (4.5 mmol) in THF (5 mL) is added. The reaction mixture is stirred at it for 45 min, then treated with 2 N aq. NaOH (2 mL). Stirring is continued for 15 min and the mixture is diluted with water (100 mL) and 1 N aq. NaOH (15 mL). The mixture is extracted with diethyl ether (70 mL). The organic extract is dried over Na2SO4 and evaporated. The crude product is purified by prep. HPLC (Waters Xterra MS18, 75×30 mm, 10 μm, 10 to 95% acetonitrile in water containing 0.5% formic acid) to give 4-phenyl-5-trifluoromethyl-thiophene-2-carboxylic acid ethyl ester (760 mg) as a brownish oil, LC-MS: tR=1.12 min; 1H NMR (CDCl3): δ 7.75-7.72 (m, 1H), 7.42 (s, 5H), 4.39 (q, J=7.0 Hz, 2H), 1.40 (t, J=7.0 Hz, 3H). is added Stirring is continued for 15 min The mixture is extracted with diethyl ether (70 mL) The organic extract is dried over Na2SO4 evaporated The crude product is purified by prep

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

実験手順: To a solution of ethyl 2-mercaptoacetate (0.88 g, 6.75 mmol) in THF (45 mL) NaH (271 mg, 6.75 mmol, 60% in mineral oil) is added at −10° C. The mixture is stirred at 0° C. for 30 min before a solution of 3-chloro-4,4,4-trifluoro-2-phenyl-but-2-enal 1.32 g (4.5 mmol) in THF (5 mL) is added. The reaction mixture is stirred at it for 45 min, then treated with 2 N aq. NaOH (2 mL). Stirring is continued for 15 min and the mixture is diluted with water (100 mL) and 1 N aq. NaOH (15 mL). The mixture is extracted with diethyl ether (70 mL). The organic extract is dried over Na2SO4 and evaporated. The crude product is purified by prep. HPLC (Waters Xterra MS18, 75×30 mm, 10 μm, 10 to 95% acetonitrile in water containing 0.5% formic acid) to give 4-phenyl-5-trifluoromethyl-thiophene-2-carboxylic acid ethyl ester (760 mg) as a brownish oil, LC-MS: tR=1.12 min; 1H NMR (CDCl3): δ 7.75-7.72 (m, 1H), 7.42 (s, 5H), 4.39 (q, J=7.0 Hz, 2H), 1.40 (t, J=7.0 Hz, 3H). is added Stirring is continued for 15 min The mixture is extracted with diethyl ether (70 mL) The organic extract is dried over Na2SO4 evaporated The crude product is purified by prep

反応条件: temp:45.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: At 0° C., DMF (4.3 mL) is carefully treated with phosphoroxychloride (2.8 mL) and the mixture is stirred at rt for 20 min before 1,1,1-trifluoro-3-phenyl-propan-2-one (1.55 mL, 10 mmol) is slowly added. The reaction mixture is stirred for 2 h at 45° C. and 18 h at rt, diluted with sat. aq. Na-acetate solution (20 mL) and water (40 mL) and extracted with diethyl ether. The organic phase is separated, washed with sat. aq. NaHCO3-solution, dried over Na2SO4 and evaporated to give 3-chloro-4,4,4-trifluoro-2-phenyl-but-2-enal (2.20 g) as a pale yellow oil. is slowly added extracted with diethyl ether The organic phase is separated washed with sat. aq. NaHCO3-solution dried over Na2SO4 evaporated

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

実験手順: To a solution of ethyl 2-mercaptoacetate (0.88 g, 6.75 mmol) in THF (45 mL) NaH (271 mg, 6.75 mmol, 60% in mineral oil) is added at −10° C. The mixture is stirred at 0° C. for 30 min before a solution of 3-chloro-4,4,4-trifluoro-2-phenyl-but-2-enal 1.32 g (4.5 mmol) in THF (5 mL) is added. The reaction mixture is stirred at it for 45 min, then treated with 2 N aq. NaOH (2 mL). Stirring is continued for 15 min and the mixture is diluted with water (100 mL) and 1 N aq. NaOH (15 mL). The mixture is extracted with diethyl ether (70 mL). The organic extract is dried over Na2SO4 and evaporated. The crude product is purified by prep. HPLC (Waters Xterra MS18, 75×30 mm, 10 μm, 10 to 95% acetonitrile in water containing 0.5% formic acid) to give 4-phenyl-5-trifluoromethyl-thiophene-2-carboxylic acid ethyl ester (760 mg) as a brownish oil, LC-MS: tR=1.12 min; 1H NMR (CDCl3): δ 7.75-7.72 (m, 1H), 7.42 (s, 5H), 4.39 (q, J=7.0 Hz, 2H), 1.40 (t, J=7.0 Hz, 3H). is added Stirring is continued for 15 min The mixture is extracted with diethyl ether (70 mL) The organic extract is dried over Na2SO4 evaporated The crude product is purified by prep

反応条件: temp:45.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: At 0° C., DMF (4.3 mL) is carefully treated with phosphoroxychloride (2.8 mL) and the mixture is stirred at rt for 20 min before 1,1,1-trifluoro-3-phenyl-propan-2-one (1.55 mL, 10 mmol) is slowly added. The reaction mixture is stirred for 2 h at 45° C. and 18 h at rt, diluted with sat. aq. Na-acetate solution (20 mL) and water (40 mL) and extracted with diethyl ether. The organic phase is separated, washed with sat. aq. NaHCO3-solution, dried over Na2SO4 and evaporated to give 3-chloro-4,4,4-trifluoro-2-phenyl-but-2-enal (2.20 g) as a pale yellow oil. is slowly added extracted with diethyl ether The organic phase is separated washed with sat. aq. NaHCO3-solution dried over Na2SO4 evaporated