ethyl 2-[bis(2,2,2-trifluoroethoxy)phosphoryl]acetate

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: 3-m-Tolyl-acrylic acid ethyl ester. (Scheme 3) KHMDS (4.0 g, 20.0 mmol) was added to a solution of ethyl[bis(2,2,2-trifluoro-ethoxy)phosphinyl]acetate (4.7 mL, 20.0 mmol) and 18-crown-6 (10.6 g, 40.0 mmol) in THF (200 mL) at −78° C., and stirred for 30 minutes. m-Tolualdehyde (2.1 mL, 18 mmol) was added and the reaction mixture was stirred for 3 hours from −78° C. to room temperature. The reaction was quenched with aqueous hydrochloric acid (1M solution, 100 mL), and the product was extracted with EtOAc (3×100 mL). The organic extracts were washed with brine (100 mL), dried over MgSO4, and concentrated to afford the subtitle compound, which was used without further purification. MS calculated for C12H14O2+H: 191, observed: 191. the reaction mixture was stirred for 3 hours from −78° C. to room temperature The reaction was quenched with aqueous hydrochloric acid (1M solution, 100 mL) the product was extracted with EtOAc (3×100 mL) The organic extracts were washed with brine (100 mL) dried over MgSO4 concentrated

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

実験手順: Potassium bis(trimethylsilyl)amide (3.92 g, 19.7 mol) was added to a solution of 18-Crown-6 (9.95 g, 37.6 mmol) and [Bis-(2,2,2 trifluoro-ethoxy)-phosphoryl]-acetic acid ethyl ester (6.54 g, 19.7 mmol) in dry THF (200 mL) at −78° C. After 30 minutes of stirring at this temperature, thiophene-3-carbaldehyde (2.0 g, 19.7 mmol) was added and the reaction was stirred for 3 hours at −78° C. after which the reaction was quenched with saturated ammonium chloride (200 mL). The reaction mixture was allowed to come to room temperature and was extracted with ethyl acetate (3×250 mL) and the combined organic extracts were washed with 10% HCl (200 mL), brine (200 mL) and dried with MgSO4 Evaporation of the solvent in vacuo gave the crude product that was purified by silica-gel chromatography using a 0-40% ethylacetate-hexane gradient to afford the subtitle compound (2.7 g, 82.7%). MS calculated for C9H10O2S +H: 183, observed: 183; 1H NMR (300 MHz, CDCl3, ppm) 1.31 (t, J=7 Hz, 3H); 4.22 (q, J=7 Hz, 2H); 5.83 (d, J=13 Hz, 1H); 6.87 (d, J=7 Hz, 1H); 7.24-7.28 (m, 1H); 7.54 (dd, J1=5 Hz, J2=1 Hz, 1H); 8.07 (br d, J=3 Hz, 1H). was added was quenched with saturated ammonium chloride (200 mL) to come to room temperature was extracted with ethyl acetate (3×250 mL) the combined organic extracts were washed with 10% HCl (200 mL), brine (200 mL) dried with MgSO4 Evaporation of the solvent in vacuo gave the crude product that was purified by silica-gel chromatography

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

実験手順: KHMDS (4.0 g, 20.0 mmol) was added to a solution of ethyl[bis(2,2,2-trifluoro-ethoxy)phosphinyl]acetate (4.7 mL, 20.0 mmol) and 18-crown-6 (10.6 g, 40.0 mmol) in THF (200 mL) at −78° C., and stirred for 30 minutes. m-Tolualdehyde (2.1 mL, 18 mmol) was added and the reaction mixture was stirred for 3 hours from −78° C. to room temperature. The reaction was quenched with aqueous hydrochloric acid (1 M solution, 100 mL), and the product was extracted with EtOAc (3×100 mL). The organic extracts were washed with brine (100 mL), dried over MgSO4, and concentrated to afford the subtitle compound, which was used without further purification. MS calculated for C12H14O2+H: 191, observed: 191. the reaction mixture was stirred for 3 hours from −78° C. to room temperature The reaction was quenched with aqueous hydrochloric acid (1 M solution, 100 mL) the product was extracted with EtOAc (3×100 mL) The organic extracts were washed with brine (100 mL) dried over MgSO4 concentrated

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

実験手順: KHMDS (4.0 g, 20.0 mmol) was added to a solution of ethyl[bis(2,2,2-trifluoro-ethoxy)phosphinyl]acetate (4.7 mL, 20.0 mmol) and 18-crown-6 (10.6 g, 40.0 mmol) in THF (200 mL) at −78° C., and stirred for 30 minutes. m-Tolualdehyde (2.1 mL, 18 mmol) was added and the reaction mixture was stirred for 3 hours from −78° C. to room temperature. The reaction was quenched with aqueous hydrochloric acid (1 M solution, 100 mL), and the product was extracted with EtOAc (3×100 mL). The organic extracts were washed with brine (100 mL), dried over MgSO4, and concentrated to afford the subtitle compound, which was used without further purification. MS calculated for C12H14O2+H: 191, observed: 191. the reaction mixture was stirred for 3 hours from −78° C. to room temperature The reaction was quenched with aqueous hydrochloric acid (1 M solution, 100 mL) the product was extracted with EtOAc (3×100 mL) The organic extracts were washed with brine (100 mL) dried over MgSO4 concentrated

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

実験手順: KHMDS (4.0 g, 20.0 mmol) was added to a solution of ethyl[bis(2,2,2-trifluoro-ethoxy)phosphinyl]acetate (4.7 mL, 20.0 mmol) and 18-crown-6 (10.6 g, 40.0 mmol) in THF (200 mL) at −78° C., and stirred for 30 minutes. m-Tolualdehyde (2.1 mL, 18 mmol) was added and the reaction mixture was stirred for 3 hours from −78° C. to room temperature. The reaction was quenched with aqueous hydrochloric acid (1M solution, 100 mL), and the product was extracted with EtOAc (3×100 mL). The organic extracts were washed with brine (100 mL), dried over MgSO4, and concentrated to afford the subtitle compound, which was used without further purification. MS calculated for C12H14O2+H: 191, observed: 191. the reaction mixture was stirred for 3 hours from −78° C. to room temperature The reaction was quenched with aqueous hydrochloric acid (1M solution, 100 mL) the product was extracted with EtOAc (3×100 mL) The organic extracts were washed with brine (100 mL) dried over MgSO4 concentrated

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

実験手順: KHMDS (4.0 g, 20.0 mmol) was added to a solution of ethyl[bis(2,2,2-trifluoro-ethoxy)phosphinyl]acetate (4.7 mL, 20.0 mmol) and 18-crown-6 (10.6 g, 40.0 mmol) in THF (200 mL) at −78° C., and stirred for 30 minutes. m-Tolualdehyde (2.1 mL, 18 mmol) was added and the reaction mixture was stirred for 3 hours from −78° C. to room temperature. The reaction was quenched with aqueous hydrochloric acid (1M solution, 100 mL), and the product was extracted with EtOAc (3×100 mL). The organic extracts were washed with brine (100 mL), dried over MgSO4, and concentrated to afford the subtitle compound, which was used without further purification. MS calculated for C12H14O2+H: 191, observed: 191. the reaction mixture was stirred for 3 hours from −78° C. to room temperature The reaction was quenched with aqueous hydrochloric acid (1M solution, 100 mL) the product was extracted with EtOAc (3×100 mL) The organic extracts were washed with brine (100 mL) dried over MgSO4 concentrated

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

実験手順: Potassium bis(trimethylsilyl)amide (3.92 g, 19.7 mol) was added to a solution of 18-Crown-6 (9.95 g, 37.6 mmol) and [Bis-(2,2,2 trifluoro-ethoxy)-phosphoryl]-acetic acid ethyl ester (6.54 g, 19.7 mmol) in dry THF (200 mL) at −78° C. After 30 minutes of stirring at this temperature, thiophene-3-carbaldehyde (2.0 g, 19.7 mmol) was added and the reaction was stirred for 3 hours at −780C after which the reaction was quenched with saturated ammonium chloride (200 mL). The reaction mixture was allowed to come to room temperature and was extracted with ethyl acetate (3×250 mL) and the combined organic extracts were washed with 10% HCl (200 mL), brine (200 mL) and dried with MgSO4 Evaporation of the solvent in vacuo gave the crude product that was purified by silica-gel chromatography using a 0-40% ethylacetate-hexane gradient to afford the subtitle compound (2.7 g, 82.7%). MS calculated for C9H10O2S+H: 183, observed: 183; 1H NMR (300 MHz, CDCl3, ppm) 1.31 (t, J=7 Hz, 3H); 4.22 (q, J=7 Hz, 2H); 5.83 (d, J=13 Hz, 1H); 6.87 (d, J=7 Hz, 1H); 7.24-7.28 (m, 1H); 7.54 (dd, J1=5 Hz, J2=1 Hz, 1H); 8.07 (br d, J=3 Hz, 1H). was added was quenched with saturated ammonium chloride (200 mL) to come to room temperature was extracted with ethyl acetate (3×250 mL) the combined organic extracts were washed with 10% HCl (200 mL), brine (200 mL) dried with MgSO4 Evaporation of the solvent in vacuo gave the crude product that was purified by silica-gel chromatography

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: Potassium bis(trimethylsilyl)amide (3.92 g, 19.7 mol) was added to a solution of 18-Crown-6 (9.95 g, 37.6 mmol) and [Bis-(2,2,2 trifluoro-ethoxy)-phosphoryl]-acetic acid ethyl ester (6.54 g, 19.7 mmol) in dry THF (200 mL) at −78° C. After 30 minutes of stirring at this temperature, thiophene-3-carbaldehyde (2.0 g, 19.7 mmol) was added and the reaction was stirred for 3 hours at −780C after which the reaction was quenched with saturated ammonium chloride (200 mL). The reaction mixture was allowed to come to room temperature and was extracted with ethyl acetate (3×250 mL) and the combined organic extracts were washed with 10% HCl (200 mL), brine (200 mL) and dried with MgSO4 Evaporation of the solvent in vacuo gave the crude product that was purified by silica-gel chromatography using a 0-40% ethylacetate-hexane gradient to afford the subtitle compound (2.7 g, 82.7%). MS calculated for C9H10O2S+H: 183, observed: 183; 1H NMR (300 MHz, CDCl3, ppm) 1.31 (t, J=7 Hz, 3H); 4.22 (q, J=7 Hz, 2H); 5.83 (d, J=13 Hz, 1H); 6.87 (d, J=7 Hz, 1H); 7.24-7.28 (m, 1H); 7.54 (dd, J1=5 Hz, J2=1 Hz, 1H); 8.07 (br d, J=3 Hz, 1H). was added was quenched with saturated ammonium chloride (200 mL) to come to room temperature was extracted with ethyl acetate (3×250 mL) the combined organic extracts were washed with 10% HCl (200 mL), brine (200 mL) dried with MgSO4 Evaporation of the solvent in vacuo gave the crude product that was purified by silica-gel chromatography

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

実験手順: In a three-necked round bottom flask, sodium hydride 60% (1.04 g, 26.0 mmol) was suspended in dimethoxyethane (15 mL) at 0° C. Ethyl[bis(2,2,2-trifluoroethoxy)phosphinyl]acetate (8.63 g, 26.0 mmol) was added and the mixture was stirred at room temperature for 15 minutes. A solution of 1-{3-(3-methoxypropoxy)-4-[(triisopropylsilyl)oxy]phenyl}ethanone (6.60 g, 17.3 mmol) and dimethoxyethane (20 mL) was added and the mixture was brought to reflux and stirred for 1 hr. The reaction mixture was hydrolyzed with saturated aqueous ammonium chloride (80 mL). The aqueous layer was extracted with ethyl acetate (3×100 mL). The combined organic layers were washed with brine, dried over anhydrous sodium sulfate, filtered and evaporated under reduced pressure. The residue was purified by flash chromatography on silica gel (cyclohexane/ethyl acetate, 8/2) to yield 7.5 g (81%) of the desired product as a colorless oil of a mixture of E and Z isomers. to reflux stirred for 1 hr The aqueous layer was extracted with ethyl acetate (3×100 mL) The combined organic layers were washed with brine dried over anhydrous sodium sulfate filtered evaporated under reduced pressure The residue was purified by flash chromatography on silica gel (cyclohexane/ethyl acetate, 8/2) to yield

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

実験手順: KHMDS (4.0 g, 20.0 mmol) was added to a solution of ethyl[bis(2,2,2-trifluoro-ethoxy)phosphinyl]acetate (4.7 mL, 20.0 mmol) and 18-crown-6 (10.6 g, 40.0 mmol) in THF (200 mL) at −78° C., and stirred for 30 minutes. m-Tolualdehyde (2.1 mL, 18 mmol) was added and the reaction mixture was stirred for 3 hours from −78° C. to room temperature. The reaction was quenched with aqueous hydrochloric acid (1 M solution, 100 mL), and the product was extracted with EtOAc (3×100 mL). The organic extracts were washed with brine (100 mL), dried over MgSO4, and concentrated to afford the subtitle compound, which was used without further purification. MS calculated for C12H14O2+H: 191, observed: 191. the reaction mixture was stirred for 3 hours from −78° C. to room temperature The reaction was quenched with aqueous hydrochloric acid (1 M solution, 100 mL) the product was extracted with EtOAc (3×100 mL) The organic extracts were washed with brine (100 mL) dried over MgSO4 concentrated