ethyl (E)-5,5,5-trifluoropent-2-enoate

反応条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 10 g (72.5 mmol) of 2,4-dihydroxybenzaldehyde, 15.3 mL (101.4 mmol) of ethyl 4-triflouromethylcrotonate, and 20 g (145 mmol) of potassium carbonate in 25 mL of anhydrous dimethylformmamide was heated to 90° C. for three h. After cooling to room temperature, the reaction was added to 500 mL of ethyl acetate. The organic phase was washed with brine three times, dried over anhydrous magnesium sulfate and concd in vacuo. Silica chromatography with EtOAc/hexane (3:7) gave 19.0 g (98%) of a yellow solid: 1H NMR (CDCl3/400 MHz) 7.63 (s, 1H), 6.85(d, J=8.8 Hz, 1H), 6.79(dd, J=8.8 Hz, 2.8 Hz, 1H), 6.70(d, J=2.8 Hz, 1H), 5.63(q, J=6.8 Hz, 1H), 4.31(m, 2H), 1.34(t, J=7.2 Hz, 3H). MS (ESI+) 289.1 (M+1, 100). After cooling to room temperature The organic phase was washed with brine three times dried over anhydrous magnesium sulfate and concd in vacuo

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

実験手順: To a stirred solution of ethyl (2E)-5,5,5-trifluoropent-2-enoate (3.0 g, 16.5 mmol) and TFA (0.38 g, 3.3 mmol) in DCM (40 mL) was added dropwise {benzyl[(trimethylsilyl)methyl]amino}methanol (7.8 g, 33 mmol) at 0° C. over a period of 30 min. After the addition, the mixture was refluxed overnight. TLC (petroleum ether:EtOAc 10:1) indicated ethyl (2E)-5,5,5-trifluoropent-2-enoate was consumed. The reaction mixture was washed with sat. NaHCO3 (40 mL), brine (40 mL), dried over Na2SO4 and concentrated in vacuo. The residue was purified by column chromatography (silica gel, petroleum ether:EtOAc=100:1 to 10:1) to give the title compound (5.1 g, 98% yield) as a yellow oil. After the addition the mixture was refluxed overnight was consumed The reaction mixture was washed with sat. NaHCO3 (40 mL), brine (40 mL) dried over Na2SO4 concentrated in vacuo The residue was purified by column chromatography (silica gel, petroleum ether:EtOAc=100:1 to 10:1)

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred suspension of NaH (60% in oil, 2.15 g, 53.5 mmol) in dry THF (50 mL) was added dropwise ethyl(diethoxyphosphoryl)acetate (11 g, 49 mmol) at 0° C. under N2 atmosphere. The resulting mixture was stirred at 0° C. for 10 min and then cooled to −70° C. A solution of 3,3,3-trifluoropropanal (5.0 g, 44.5 mmol) in dry THF (50 mL) was added to the mixture at −70° C. After the addition, the stirred mixture was allowed to warm to −20° C. over 2 hrs. The reaction mixture was quenched by addition of 5% aqueous NH4Cl (100 mL) at 0° C. and extracted with EtOAc (100 mL). The organic layer was washed with brine (300 mL), dried over Na2SO4 and concentrated in vacuo. The residue was purified by column chromatography (silica gel, petroleum ether: EtOAc=100:1) to give the title compound (3.0 g, 37%) as a colorless oil. cooled to −70° C After the addition to warm to −20° C. over 2 hrs The reaction mixture was quenched by addition of 5% aqueous NH4Cl (100 mL) at 0° C. extracted with EtOAc (100 mL) The organic layer was washed with brine (300 mL) dried over Na2SO4 concentrated in vacuo The residue was purified by column chromatography (silica gel, petroleum ether: EtOAc=100:1)

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred suspension of NaH (60% in oil, 2.15 g, 53.5 mmol) in dry THF (50 mL) was added dropwise ethyl(diethoxyphosphoryl)acetate (11 g, 49 mmol) at 0° C. under N2 atmosphere. The resulting mixture was stirred at 0° C. for 10 min and then cooled to −70° C. A solution of 3,3,3-trifluoropropanal (5.0 g, 44.5 mmol) in dry THF (50 mL) was added to the mixture at −70° C. After the addition, the stirred mixture was allowed to warm to −20° C. over 2 hrs. The reaction mixture was quenched by addition of 5% aqueous NH4Cl (100 mL) at 0° C. and extracted with EtOAc (100 mL). The organic layer was washed with brine (300 mL), dried over Na2SO4 and concentrated in vacuo. The residue was purified by column chromatography (silica gel, petroleum ether: EtOAc=100:1) to give the title compound (3.0 g, 37%) as a colorless oil. cooled to −70° C After the addition to warm to −20° C. over 2 hrs The reaction mixture was quenched by addition of 5% aqueous NH4Cl (100 mL) at 0° C. extracted with EtOAc (100 mL) The organic layer was washed with brine (300 mL) dried over Na2SO4 concentrated in vacuo The residue was purified by column chromatography (silica gel, petroleum ether: EtOAc=100:1)

反応条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 10 g (72.5 mmol) of 2,4-dihydroxybenzaldehyde, 15.3 mL (101.4 mmol) of ethyl 4-triflouromethylcrotonate, and 20 g (145 mmol) of potassium carbonate in 25 mL of anhydrous dimethylformmamide was heated to 90° C. for three h. After cooling to room temperature, the reaction was added to 500 mL of ethyl acetate. The organic phase was washed with brine three times, dried over anhydrous magnesium sulfate and concd in vacuo. Silica chromatography with EtOAc/hexane (3:7) gave 19.0 g (98%) of a yellow solid: 1H NMR (CDCl3/400 MHz) 7.63 (s, 1H), 6.85(d, J=8.8 Hz, 1H), 6.79(dd, J=8.8 Hz, 2.8 Hz, 1H), 6.70(d, J=2.8 Hz, 1H), 5.63(q, J=6.8 Hz, 1H), 4.31(m, 2H), 1.34(t, J=7.2 Hz, 3H). MS (ESI+) 289.1 (M+1, 100). After cooling to room temperature The organic phase was washed with brine three times dried over anhydrous magnesium sulfate and concd in vacuo

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

実験手順: To a stirred solution of ethyl (2E)-5,5,5-trifluoropent-2-enoate (3.0 g, 16.5 mmol) and TFA (0.38 g, 3.3 mmol) in DCM (40 mL) was added dropwise {benzyl[(trimethylsilyl)methyl]amino}methanol (7.8 g, 33 mmol) at 0° C. over a period of 30 min. After the addition, the mixture was refluxed overnight. TLC (petroleum ether:EtOAc 10:1) indicated ethyl (2E)-5,5,5-trifluoropent-2-enoate was consumed. The reaction mixture was washed with sat. NaHCO3 (40 mL), brine (40 mL), dried over Na2SO4 and concentrated in vacuo. The residue was purified by column chromatography (silica gel, petroleum ether:EtOAc=100:1 to 10:1) to give the title compound (5.1 g, 98% yield) as a yellow oil. After the addition the mixture was refluxed overnight was consumed The reaction mixture was washed with sat. NaHCO3 (40 mL), brine (40 mL) dried over Na2SO4 concentrated in vacuo The residue was purified by column chromatography (silica gel, petroleum ether:EtOAc=100:1 to 10:1)

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred suspension of NaH (60% in oil, 2.15 g, 53.5 mmol) in dry THF (50 mL) was added dropwise ethyl(diethoxyphosphoryl)acetate (11 g, 49 mmol) at 0° C. under N2 atmosphere. The resulting mixture was stirred at 0° C. for 10 min and then cooled to −70° C. A solution of 3,3,3-trifluoropropanal (5.0 g, 44.5 mmol) in dry THF (50 mL) was added to the mixture at −70° C. After the addition, the stirred mixture was allowed to warm to −20° C. over 2 hrs. The reaction mixture was quenched by addition of 5% aqueous NH4Cl (100 mL) at 0° C. and extracted with EtOAc (100 mL). The organic layer was washed with brine (300 mL), dried over Na2SO4 and concentrated in vacuo. The residue was purified by column chromatography (silica gel, petroleum ether: EtOAc=100:1) to give the title compound (3.0 g, 37%) as a colorless oil. cooled to −70° C After the addition to warm to −20° C. over 2 hrs The reaction mixture was quenched by addition of 5% aqueous NH4Cl (100 mL) at 0° C. extracted with EtOAc (100 mL) The organic layer was washed with brine (300 mL) dried over Na2SO4 concentrated in vacuo The residue was purified by column chromatography (silica gel, petroleum ether: EtOAc=100:1)