5-bromo-1-benzofuran-3-one

反応条件: temp:0.00; pressure:0.00; stir:

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

実験手順: To a solution of triethyl phosphonoacetate (6 ml, 30.2 mmol) in dry tetrahydrofuran (200 ml) at -78° C. was added a solution of potassium bis(trimethylsilyl)amide in toluene (58 ml of a 0.5M solution). After stirring for 2 hours at -78° C., 5-bromobenzofuran-3-one (5.5 g, 26 mmol) was added dropwise. The resulting solution was stirred 1 hour at -78° C. and overnight at room temperature. Saturated aqueous ammonium chloride solution and ethyl acetate were added. The organic layer was separated and evaporated to dryness to give the crude title compound which was purified by column chromatography on silica using dichloromethane, followed by column chromatography on alumina using dichloromethane. 5-Bromobenzofuran-3-ylacetic acid ethyl ester was obtained as a low melting solid (4.2 g, 57%). mp 38-40° C. 1H NMR (250 MHz, CDCl3) δ 1.28 (3H, t, J=7 Hz), 3.65 (2H, d, J=1 Hz), 4.20 (2H, q, J=7 Hz), 7.36 (1H, s), 7.38 (1H, d, J=2 Hz), 7.63 (1H, s), 7.71 (1H, d, J=2 Hz). The resulting solution was stirred 1 hour at -78° C. and overnight at room temperature The organic layer was separated evaporated to dryness to give the crude title compound which was purified by column chromatography on silica

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Cesium carbonate (612 mg, 1.88 mmol) was added to a solution of 5-bromobenzofuran-3(2H)-one (200 mg, 0.939 mmol), (3-fluorophenyl)boronic acid (263 mg, 1.88 mmol) and toluene (20 mL) in a 50 mL Schlenk tube. A nitrogen atmosphere was established by evacuating and refilling with nitrogen (3×), then tetrakis(triphenylphosphine)palladium (0) (11 mg, 0.01 mmol) was added to the reaction. The flask was sealed and heated in a 80° C. oil bath overnight. The resulting mixture was cooled to room temperature. The reaction was then diluted with ethyl acetate and filtered through celite. Ethyl acetate (30 mL) was used to wash the flask and the combined organic filtrate was concentrated. The resulting crude residue was purified on a Teledyne-Isco Combiflash machine (40 g column, hexanes→100% ethyl acetate/hexanes, gradient), to afford 212 mg (99%) of 5-(3-fluorophenyl)benzofuran-3(2H)-one. by evacuating The flask was sealed The resulting mixture was cooled to room temperature filtered through celite to wash the flask the combined organic filtrate was concentrated The resulting crude residue was purified on a Teledyne-Isco Combiflash machine (40 g column, hexanes→100% ethyl acetate/hexanes, gradient)

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

実験手順: Potassium carbonate (1.66 g, 12 mmol) is added to a solution of 5-bromo-1-benzofuran-3(2H)-one (2.13 g, 10 mmol) in acetone (25 mL). The stirred mixture is treated dropwise with ethyl chloroformate (1.05 mL, 11 mmol). The mixture is then heated at reflux for 18 h. The solids are filtered off and the filtrate concentrated in vacuo. The residue is partitioned between EtOAc and saturated aqueous NaHCO3. The layers are separated and the organic layer washed with brine, dried (Na2SO4), filtered and concentrated in vacuo. The residue is purified by silica gel chromatography (gradient elution with hexanes-EtOAc) to afford the title compound. The mixture is then heated at reflux for 18 h The solids are filtered off the filtrate concentrated in vacuo The residue is partitioned between EtOAc and saturated aqueous NaHCO3 The layers are separated the organic layer washed with brine dried (Na2SO4) filtered concentrated in vacuo The residue is purified by silica gel chromatography (gradient elution with hexanes-EtOAc)

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

実験手順: To a solution of triethyl phosphonoacetate (6 ml, 30.2 mmol) in dry tetrahydrofuran (200 ml) at -78° C. was added a solution of potassium bis(trimethylsilyl)amide in toluene (58 ml of a 0.5 M solution). After stirring for 2 hours at -78° C., 5-bromobenzofuran-3-one (5.5 g, 26 mmol) was added dropwise. The resulting solution was stirred 1 hour at -78° C. and overnight at room temperature. Saturated aqueous ammonium chloride solution and ethyl acetate were added. The organic layer was separated and evaporated to dryness to give the crude title compound which was purified by column chromatography on silica using chloromethane, followed by column chromatography on alumina using dichloromethane. (5-Bromobenzofuran-3-yl)acetic acid ethyl ester was obtained as a low melting solid (4.2 g, 57%), mp 38-40° C. 1H NMR 250 MHz, CDCl3) δ1.28 (3H, t, J=7 Hz), 3.65 (2H, d, J=1 Hz), 4.20 (2H, q, J=7 Hz), 7.36 (1H, s), 7.38 (1H, d, J=2 Hz), 7.63 (1H, s), 7.71 (1H, d, J=2 Hz). The resulting solution was stirred 1 hour at -78° C. and overnight at room temperature The organic layer was separated evaporated to dryness to give the crude title compound which was purified by column chromatography on silica

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

実験手順: To a solution of triethyl phosphonoacetate (6 ml, 30.2 mmol) in dry tetrahydrofuran (200 ml) at -78° C. was added a solution of potassium bis(trimethylsilyl)amide in toluene (58 ml of a 0.5M solution). After stirring for 2 hours at -78° C., 5-bromobenzofuran-3-one (5.5 g, 26 mmol) was added dropwise. The resulting solution was stirred 1 hour at -78° C. and overnight at room temperature. Saturated aqueous ammonium chloride solution and ethyl acetate were added. The organic layer was separated and evaporated to dryness to give the crude title compound which was purified by column chromatography on silica using dichloromethane, followed by column chromatography on alumina using dichloromethane. 5-Bromobenzofuran-3-ylacetic acid ethyl ester was obtained as a low melting solid (4.2 g, 57%). mp 38-40° C. 1H NMR (250 MHz, CDCl3) δ 1.28 (3H, t, J=7 Hz), 3.65 (2H, d, J=1 Hz), 4.20 (2H, q, J=7 Hz), 7.36 (1H, s), 7.38 (1H, d, J=2 Hz), 7.63 (1H, s), 7.71 (1H, d, J=2 Hz). The resulting solution was stirred 1 hour at -78° C. and overnight at room temperature The organic layer was separated evaporated to dryness to give the crude title compound which was purified by column chromatography on silica

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

実験手順: To a solution of triethyl phosphonoacetate (6 ml, 30.2 mmol) in dry tetrahydrofuran (200 ml) at -78° C. was added a solution of potassium bis(trimethylsilyl)amide in toluene (58 ml of a 0.5M solution). After stirring for 2 hours at -78° C., 5-bromobenzofuran-3-one (5.5 g, 26 mmol) was added dropwise. The resulting solution was stirred 1 hour at -78° C. and overnight at room temperature. Saturated aqueous ammonium chloride solution and ethyl acetate were added. The organic layer was separated and evaporated to dryness to give the crude title compound which was purified by column chromatography on silica using dichloromethane, followed by column chromatography on alumina using dichloromethane. 5-Bromobenzofuran-3-ylacetic acid ethyl ester was obtained as a low melting solid (4.2 g, 57%). mp 38-40° C. 1H NMR (250 MHz, CDCl3) δ 1.28 (3H, t, J=7 Hz), 3.65 (2H, d, J=1 Hz), 4.20 (2H, q, J=7 Hz), 7.36 (1H, s), 7.38 (1H, d, J=2 Hz), 7.63 (1H, s), 7.71 (1H, d, J=2 Hz). The resulting solution was stirred 1 hour at -78° C. and overnight at room temperature The organic layer was separated evaporated to dryness to give the crude title compound which was purified by column chromatography on silica

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: Dimethyl [2-(dimethylamino)-2-oxoethyl]phosphonate (5 g) was added to a stirred suspension of sodium hydride (1.02 g of a 60% dispersion in oil) in dry THF (100 ml) at 0° under nitrogen. After stirring for 15 minutes 5-bromo-3-(2H)-benzofuranone (5.0 g) in THF (20 ml) was added dropwise and stirred at room temperature for 3 h. Water (50 ml) was added and the mixture extracted with ethyl acetate (3×50 ml), dried and the solvent removed in vacuo. The crude material was purified by flash chromatography using 50% ethyl acetate/hexane as eluant to yield the title compound as a pale yellow solid m.p. 92°-94° C. was added dropwise the mixture extracted with ethyl acetate (3×50 ml) dried the solvent removed in vacuo The crude material was purified by flash chromatography

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

実験手順: Dimethyl [2-(dimethylamino)-2-oxoethyl]phosphonate (5 g) was added to a stirred suspension of sodium hydride (1.02 g of a 60% dispersion in oil) in dry THF (100 ml) at 0° under nitrogen. After stirring for 15 minutes 5-bromo-3-(2H)-benzofuranone (5.0 g) in THF (20 ml) was added dropwise and stirred at room temperature for 3 h. Water (50 ml) was added and the mixture extracted with ethyl acetate (3×50 ml), dried and the solvent removed in vacuo. The crude material was purified by flash chromatography using 50% ethyl acetate/hexane as eluant to yield the title compound as a pale yellow solid m.p. 92°-94° C. was added dropwise the mixture extracted with ethyl acetate (3×50 ml) dried the solvent removed in vacuo The crude material was purified by flash chromatography

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

実験手順: Dimethyl [2-(dimethylamino)-2-oxoethyl]phosphonate (5 g) was added to a stirred suspension of sodium hydride (1.02 g of a 60% dispersion in oil) in dry THF (100 ml) at 0° under nitrogen. After stirring for 15 minutes 5-bromo-3-(2H)-benzofuranone (5.0 g) in THF (20 ml) was added dropwise and stirred at room temperature for 3 h. Water (50 ml) was added and the mixture extracted with ethyl acetate (3×50 ml), dried and the solvent removed in vacuo. The crude material was purified by flash chromatography using 50% ethyl acetate/hexane as eluant to yield the title compound as a pale yellow solid m.p. 92°-94° C. was added dropwise the mixture extracted with ethyl acetate (3×50 ml) dried the solvent removed in vacuo The crude material was purified by flash chromatography

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

実験手順: A suspension of 5-bromo-3-(2H)-benzofuranone (4.26 g) and cyanomethylene triphenylphosphorane (9.06 g) in dry xylene (100 ml) was heated at reflux for 24 h . A further quantity of the phosphorane (450 mg) was added and heating continued for a further period of 12 h. On cooling to ambient temperature the brown coloured suspension was evaporated to dryness in vacuo. Chromatography of the residue using dichloromethane:hexane (1:3) as eluant afforded a cream coloured product. Recrystallization (from ethanol) of the chromatographed material afforded the title compound as cream flakes, m.p. 120°. was heated at reflux for 24 h heating was evaporated to dryness in vacuo afforded a cream coloured product Recrystallization (from ethanol) of the chromatographed material