1-trimethylsilylethanone

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

実験手順: A suspension of ground LaCl3 (26 mg, 0.104 mmol) in dry THF (7.8 mL) under N2 was cooled to −78° C. and stirred for 15 min. A solution of n-BuLi (1.6 M in hexanes, 195 μL, 0.312 mmol) was added and stirring was continued for 15 min. The reaction was warmed to 0° C. and stirred for 30 min. Trimethylsilyl cyanide (31 mg, 42 μL, 0.312 mmol) was added and the reaction was stirred for 30 min at 0° C. and warmed to room temperature over 30 min. A solution of acetyltrimethylsilane (Cunico, R. F., Kuan, C.-P., J. Org. Chem., 1985, 50, 5410-5413) (121 mg, 1.04 mmol) and 4-fluorobenzaldehyde (142 mg, 1.14 mmol) in dry THF (19 mL) was added by cannula and the reaction was stirred at room temperature for 2 h. After this time 1N HCl (24 mL) was added and the reaction was stirred for 1 h. Et2O (25 mL) was added and the organic layer was separated and washed with H2O (2×25 mL). The combined aqueous layers were extracted with Et2O (3×50 mL). The combined organic extracts were dried (MgSO4) and concentrated in vacuo to give the crude product. This was purified by flash chromatography (Si, 25×160 mm, 0-50% EtOAc in hexanes gradient) to give 1-(4-fluorophenyl)-1-hydroxyacetone as a colorless solid. Rf=0.31 (20% EtOAc/hexanes). 1H NMR (CDCl3, 500 MHz) δ 7.29 (m, 2H), 7.08-7.04 (m, 2H), 5.06 (d, J=3.6 Hz, 1H), 4.35 (t, J=6.5 Hz, 1H), 2.05 (s, 3H). stirring was continued for 15 min The reaction was warmed to 0° C. stirred for 30 min the reaction was stirred for 30 min at 0° C. warmed to room temperature over 30 min the reaction was stirred at room temperature for 2 h the reaction was stirred for 1 h the organic layer was separated washed with H2O (2×25 mL) The combined aqueous layers were extracted with Et2O (3×50 mL) The combined organic extracts were dried (MgSO4) concentrated in vacuo to give the crude product This was purified by flash chromatography (Si, 25×160 mm, 0-50% EtOAc in hexanes gradient)

反応条件: temp:95.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a mixture of acetyltrimethylsilane (1.0 g, 8.6 mmol), malononitrile (625 mg, 9.46 mmol) and ammonium acetate (126 mg, 1.64 mmol), acetic acid (394 μL, 6.88 mmol) and benzene (30 mL) were added. The reaction flask was attached to a Dean-Stark trap filled with benzene and the solution was heated to 95° C. for 3 h. The orange reaction mixture was cooled, diluted with EtOAc, washed with saturated aqueous NaHCO3 and brine, dried over anhydrous MgSO4, and concentrated. The residue was purified by column chromatography on silica gel (using a solvent gradient from 1% to 30% EtOAc in hexanes) to give 2-(1-(trimethylsilyl)ethylidene) malononitrile as colorless oil (1.13 g, 79.8%). were added The orange reaction mixture was cooled washed with saturated aqueous NaHCO3 and brine dried over anhydrous MgSO4 concentrated The residue was purified by column chromatography on silica gel (

反応条件: temp:95.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a mixture of acetyltrimethylsilane (1.0 g, 8.6 mmol), malononitrile (625 mg, 9.46 mmol) and ammonium acetate (126 mg, 1.64 mmol), acetic acid (394 μL, 6.88 mmol) and benzene (30 mL) were added. The reaction flask was attached to a Dean-Stark trap filled with benzene and the solution was heated to 95° C. for 3 h. The orange reaction mixture was cooled, diluted with EtOAc, washed with saturated aqueous NaHCO3 and brine, dried over anhydrous MgSO4, and concentrated. The residue was purified by column chromatography on silica gel (using a solvent gradient from 1% to 30% EtOAc in hexanes) to give 2-(1-(trimethylsilyl)ethylidene) malononitrile as colorless oil (1.13 g, 79.8%). were added The orange reaction mixture was cooled washed with saturated aqueous NaHCO3 and brine dried over anhydrous MgSO4 concentrated The residue was purified by column chromatography on silica gel (

反応条件: temp:95.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a mixture of acetyltrimethylsilane (1.0 g, 8.6 mmol), malononitrile (625 mg, 9.46 mmol) and ammonium acetate (126 mg, 1.64 mmol), acetic acid (394 μL, 6.88 mmol) and benzene (30 mL) were added. The reaction flask was attached to a Dean-Stark trap filled with benzene and the solution was heated to 95° C. for 3 h. The orange reaction mixture was cooled, diluted with EtOAc, washed with saturated aqueous NaHCO3 and brine, dried over anhydrous MgSO4, and concentrated. The residue was purified by column chromatography on silica gel (using a solvent gradient from 1% to 30% EtOAc in hexanes) to give 2-(1-(trimethylsilyl)ethylidene) malononitrile as colorless oil (1.13 g, 79.8%). were added The orange reaction mixture was cooled washed with saturated aqueous NaHCO3 and brine dried over anhydrous MgSO4 concentrated The residue was purified by column chromatography on silica gel (

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

実験手順: 1-Trimethylsilanyl-ethanone (1.15 mL; 8.02 mmol) followed by DBU (0.18 mL; 1.2 mmol) were added to a suspension of 3-ethyl-5-(2-hydroxyethyl)-4-methylthiazolium bromide (304 mg; 1.21 mmol) in dry THF (5 mL). The mixture was heated at 70° C. for 4 min, cooled near rt, then chalcone (833 mg; 4.00 mmol) and 2-propanol (1.22 mL; 15.9 mmol) were added. The reaction was degassed and reacted under nitrogen at 70° C. After 24 h, the reaction was concentrated on a rotary evaporator. Ethyl acetate (25 mL) was added and this washed with H2O (3×3 mL) and satd NaCl (2×3 mL). The organic portion was dried (MgSO4) and filtered through silica with an EtOAc wash. Crude product was adsorbed onto silica (2 g) then purified by MPLC (40 g of silica using a 0→20% EtOAc in hexanes gradient). Pure product was obtained as a clear, colorless viscous liquid (980 mg; 97%). 1H NMR (CDCl3) δ 7.98-7.94 (m, 2H), 7.56 (m, 1H), 7.47-7.42 (m, 2H), 7.39-7.27 (m, 5H), 4.44 (dd, J=3.6, 10.0 Hz, 1H), 4.02 (dd, J=10.0, 18.0 Hz, 1H), 3.14 (dd, J=3.6, 18.0 Hz, 1H); GC-MS 252 ([M]+). cooled near rt The reaction was degassed reacted under nitrogen at 70° C the reaction was concentrated on a rotary evaporator Ethyl acetate (25 mL) was added this washed with H2O (3×3 mL) and satd NaCl (2×3 mL) The organic portion was dried (MgSO4) filtered through silica with an EtOAc wash then purified by MPLC (40 g of silica using a 0→20% EtOAc in hexanes gradient) Pure product was obtained as a clear, colorless viscous liquid (980 mg; 97%)

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

実験手順: 1-Trimethylsilanyl-ethanone (1.15 mL; 8.02 mmol) followed by DBU (0.18 mL; 1.2 mmol) were added to a suspension of 3-ethyl-5-(2-hydroxyethyl)-4-methylthiazolium bromide (304 mg; 1.21 mmol) in dry THF (5 mL). The mixture was heated at 70° C. for 4 min, cooled near rt, then chalcone (833 mg; 4.00 mmol) and 2-propanol (1.22 mL; 15.9 mmol) were added. The reaction was degassed and reacted under nitrogen at 70° C. After 24 h, the reaction was concentrated on a rotary evaporator. Ethyl acetate (25 mL) was added and this washed with H2O (3×3 mL) and satd NaCl (2×3 mL). The organic portion was dried (MgSO4) and filtered through silica with an EtOAc wash. Crude product was adsorbed onto silica (2 g) then purified by MPLC (40 g of silica using a 0→20% EtOAc in hexanes gradient). Pure product was obtained as a clear, colorless viscous liquid (980 mg; 97%). 1H NMR (CDCl3) δ 7.98-7.94 (m, 2H), 7.56 (m, 1H), 7.47-7.42 (m, 2H), 7.39-7.27 (m, 5H), 4.44 (dd, J=3.6, 10.0 Hz, 1H), 4.02 (dd, J=10.0, 18.0 Hz, 1H), 3.14 (dd, J=3.6, 18.0 Hz, 1H); GC-MS 252 ([M]+). cooled near rt The reaction was degassed reacted under nitrogen at 70° C the reaction was concentrated on a rotary evaporator Ethyl acetate (25 mL) was added this washed with H2O (3×3 mL) and satd NaCl (2×3 mL) The organic portion was dried (MgSO4) filtered through silica with an EtOAc wash then purified by MPLC (40 g of silica using a 0→20% EtOAc in hexanes gradient) Pure product was obtained as a clear, colorless viscous liquid (980 mg; 97%)

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

実験手順: A suspension of ground LaCl3 (26 mg, 0.104 mmol) in dry THF (7.8 mL) under N2 was cooled to −78° C. and stirred for 15 min. A solution of n-BuLi (1.6 M in hexanes, 195 μL, 0.312 mmol) was added and stirring was continued for 15 min. The reaction was warmed to 0° C. and stirred for 30 min. Trimethylsilyl cyanide (31 mg, 42 μL, 0.312 mmol) was added and the reaction was stirred for 30 min at 0° C. and warmed to room temperature over 30 min. A solution of acetyltrimethylsilane (Cunico, R. F., Kuan, C.-P., J. Org. Chem., 1985, 50, 5410-5413) (121 mg, 1.04 mmol) and 4-fluorobenzaldehyde (142 mg, 1.14 mmol) in dry THF (19 mL) was added by cannula and the reaction was stirred at room temperature for 2 h. After this time 1N HCl (24 mL) was added and the reaction was stirred for 1 h. Et2O (25 mL) was added and the organic layer was separated and washed with H2O (2×25 mL). The combined aqueous layers were extracted with Et2O (3×50 mL). The combined organic extracts were dried (MgSO4) and concentrated in vacuo to give the crude product. This was purified by flash chromatography (Si, 25×160 mm, 0-50% EtOAc in hexanes gradient) to give 1-(4-fluorophenyl)-1-hydroxyacetone as a colorless solid. Rf=0.31 (20% EtOAc/hexanes). 1H NMR (CDCl3, 500 MHz) δ 7.29 (m, 2H), 7.08-7.04 (m, 2H), 5.06 (d, J=3.6 Hz, 1H), 4.35 (t, J=6.5 Hz, 1H), 2.05 (s, 3H). stirring was continued for 15 min The reaction was warmed to 0° C. stirred for 30 min the reaction was stirred for 30 min at 0° C. warmed to room temperature over 30 min the reaction was stirred at room temperature for 2 h the reaction was stirred for 1 h the organic layer was separated washed with H2O (2×25 mL) The combined aqueous layers were extracted with Et2O (3×50 mL) The combined organic extracts were dried (MgSO4) concentrated in vacuo to give the crude product This was purified by flash chromatography (Si, 25×160 mm, 0-50% EtOAc in hexanes gradient)

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

実験手順: 1-Trimethylsilanyl-ethanone (1.15 mL; 8.02 mmol) followed by DBU (0.18 mL; 1.2 mmol) were added to a suspension of 3-ethyl-5-(2-hydroxyethyl)-4-methylthiazolium bromide (304 mg; 1.21 mmol) in dry THF (5 mL). The mixture was heated at 70° C. for 4 min, cooled near rt, then chalcone (833 mg; 4.00 mmol) and 2-propanol (1.22 mL; 15.9 mmol) were added. The reaction was degassed and reacted under nitrogen at 70° C. After 24 h, the reaction was concentrated on a rotary evaporator. Ethyl acetate (25 mL) was added and this washed with H2O (3×3 mL) and satd NaCl (2×3 mL). The organic portion was dried (MgSO4) and filtered through silica with an EtOAc wash. Crude product was adsorbed onto silica (2 g) then purified by MPLC (40 g of silica using a 0→20% EtOAc in hexanes gradient). Pure product was obtained as a clear, colorless viscous liquid (980 mg; 97%). 1H NMR (CDCl3) d 7.98-7.94 (m, 2H), 7.56 (m, 1H), 7.47-7.42 (m, 2H), 7.39-7.27 (m, 5H), 4.44 (dd, J=3.6, 10.0 Hz, 1H), 4.02 (dd, J=10.0, 18.0 Hz, 1H), 3.14 (dd, J=3.6, 18.0 Hz, 1H); GC-MS 252 ([M]+). cooled near rt The reaction was degassed reacted under nitrogen at 70° C the reaction was concentrated on a rotary evaporator Ethyl acetate (25 mL) was added this washed with H2O (3×3 mL) and satd NaCl (2×3 mL) The organic portion was dried (MgSO4) filtered through silica with an EtOAc wash then purified by MPLC (40 g of silica using a 0→20% EtOAc in hexanes gradient) Pure product was obtained as a clear, colorless viscous liquid (980 mg; 97%)

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

実験手順: A suspension of ground LaCl3 (26 mg, 0.104 mmol) in dry THF (7.8 mL) under N2 was cooled to −78° C. and stirred for 15 min. A solution of n-BuLi (1.6 M in hexanes, 195 μL, 0.312 mmol) was added and stirring was continued for 15 min. The reaction was warmed to 0° C. and stirred for 30 min. Trimethylsilyl cyanide (31 mg, 42 μL, 0.312 mmol) was added and the reaction was stirred for 30 min at 0° C. and warmed to room temperature over 30 min. A solution of acetyltrimethylsilane (Cunico, R. F., Kuan, C.-P., J. Org. Chem., 1985, 50, 5410-5413) (121 mg, 1.04 mmol) and 4-fluorobenzaldehyde (142 mg, 1.14 mmol) in dry THF (19 mL) was added by cannula and the reaction was stirred at room temperature for 2 h. After this time 1N HCl (24 mL) was added and the reaction was stirred for 1 h. Et2O (25 mL) was added and the organic layer was separated and washed with H2O (2×25 mL). The combined aqueous layers were extracted with Et2O (3×50 mL). The combined organic extracts were dried (MgSO4) and concentrated in vacuo to give the crude product. This was purified by flash chromatography (Si, 25×160 mm, 0-50% EtOAc in hexanes gradient) to give 1-(4-fluorophenyl)-1-hydroxyacetone as a colorless solid. Rf=0.31 (20% EtOAc/hexanes). 1H NMR (CDCl3, 500 MHz) δ 7.29 (m, 2H), 7.08-7.04 (m, 2H), 5.06 (d, J=3.6 Hz, 1H), 4.35 (t, J=6.5 Hz, 1H), 2.05 (s, 3H). stirring was continued for 15 min The reaction was warmed to 0° C. stirred for 30 min the reaction was stirred for 30 min at 0° C. warmed to room temperature over 30 min the reaction was stirred at room temperature for 2 h the reaction was stirred for 1 h the organic layer was separated washed with H2O (2×25 mL) The combined aqueous layers were extracted with Et2O (3×50 mL) The combined organic extracts were dried (MgSO4) concentrated in vacuo to give the crude product This was purified by flash chromatography (Si, 25×160 mm, 0-50% EtOAc in hexanes gradient)

反応条件: temp:95.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a mixture of acetyltrimethylsilane (1.0 g, 8.6 mmol), malononitrile (625 mg, 9.46 mmol) and ammonium acetate (126 mg, 1.64 mmol), acetic acid (394 μL, 6.88 mmol) and benzene (30 mL) were added. The reaction flask was attached to a Dean-Stark trap filled with benzene and the solution was heated to 95° C. for 3 h. The orange reaction mixture was cooled, diluted with EtOAc, washed with saturated aqueous NaHCO3 and brine, dried over anhydrous MgSO4, and concentrated. The residue was purified by column chromatography on silica gel (using a solvent gradient from 1% to 30% EtOAc in hexanes) to give 2-(1-(trimethylsilyl)ethylidene) malononitrile as colorless oil (1.13 g, 79.8%). were added The orange reaction mixture was cooled washed with saturated aqueous NaHCO3 and brine dried over anhydrous MgSO4 concentrated The residue was purified by column chromatography on silica gel (