1-(1-benzofuran-3-yl)ethanone

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 2-methoxyphenylacetone (5 g, 30.5 mmol) in N,N-dimethylformamide dimethyl acetal (8.7 ml, 73.1 mmol) was stirred at 80° C. for 4 hours. The mixture was concentrated under vacuum. The resulting residue was dissolved in dichloromethane (40 ml), cooled to 0° C. and treated with a solution of boron tribromide (5 ml, 52.9 mmol) in dichloromethane (10 ml). After stirring at 0° C. for 1 hour, additional boron tribromide (5 ml, 52.9 mmol) was added. The mixture was stirred at 0° C. for 10 more minutes and was poured into a mixture of ice and saturated aqueous sodium bicarbonate. The resulting mixture was extracted with dichloromethane three times. The combined organic extracts were washed with water once and dried over anhydrous sodium sulfate to give 3-acetylbenzofuran (4.7 g, 96%, 94.5% AUC HPLC): 1H NMR (300 MHz, CDCl3) δ 8.16-8.19 (m, 2H), 7.44-7.48 (m, 1H), 7.29-7.32 (m, 2H), 2.50 (s, 3H). The mixture was concentrated under vacuum The resulting residue was dissolved in dichloromethane (40 ml) The mixture was stirred at 0° C. for 10 more minutes The resulting mixture was extracted with dichloromethane three times The combined organic extracts were washed with water once dried over anhydrous sodium sulfate

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 1-(2-methoxyphenyl)propan-2-one (77.2 g) and dimethylformamide dimethyl acetal (137.5 g) was stirred at 80° C. under nitrogen for 4 hours, then concentrated in vacuo to leave a viscous oil. The oil was dissolved in dichloromethane (620 ml) then the stirred solution was cooled to 0° C. Boron tribromide (1M solution in dichloromethane, 800 ml) was added dropwise over 1.75 hours at 0°-5° C., then the mixture was stirred at 0°-5° C. for a further 1.5 hours and poured onto an excess of ice and saturated aqueous sodium hydrogen carbonate solution. Solid sodium hydrogen carbonate was added in portions with occasional stirring until effervescence ceased. The product was extracted into dichloromethane (3×600 ml) then the combined extracts were washed with water (2×600 ml), dried (Na2SO4), and the solvent removed in vacuo to leave 3-acetylbenzo[b]furan as a brown oil (78.9 g). concentrated in vacuo to leave a viscous oil the stirred solution was cooled to 0° C the mixture was stirred at 0°-5° C. for a further 1.5 hours with occasional stirring until effervescence The product was extracted into dichloromethane (3×600 ml) the combined extracts were washed with water (2×600 ml) dried (Na2SO4) the solvent removed in vacuo

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of phenyltrimethylammonium tribromide (2.47 g) in tetrahydrofuran (20 ml) was added dropwise at ambient temperature under nitrogen over 5 minutes to a stirred solution of 3-acetylbenzo[b]furan (1 g) in tetrahydrofuran (20 ml), then the mixture was stirred at ambient temperature for a further 1.5 hours, filtered, and the solvent removed in vacuo. The residue was triturated with ether, and the resulting solid was collected by filtration and dried in vacuo at ambient temperature to give 3-(2-bromoacetyl)benzo[b]furan as an off-white solid (0.25 g). filtered the solvent removed in vacuo The residue was triturated with ether the resulting solid was collected by filtration dried in vacuo at ambient temperature

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 1-(2-methoxyphenyl)propan-2-one (10 g) and dimethylformamide dimethyl acetal (17.8 g) was stirred at 80° C, under nitrogen for 4 hours, then concentrated in vacuo to leave a viscous oil. The oil was disolved in dichloromethane (80 ml), and the solution was stirred and cooled in an ice-bath while boron tribromide (1M solution in dichloromethane; 104 ml) was added dropwise over 15 minutes. When the addition was complete, the mixture was stirred, with ice-cooling, for a further 1.5 hours, then it was poured into an excess of ice and saturated aqueous sodium hydrogen carbonate solution. The product was extracted into dichloromethane (3×200 ml) and the combined extracts were washed with water (2×200 ml), dried (Na2SO4), and the solvent removed in vacuo to leave 3-acetylbenzo[b]furan as a dark red oil (4.25 g). concentrated in vacuo to leave a viscous oil the solution was stirred was added dropwise over 15 minutes When the addition the mixture was stirred, with ice- cooling, for a further 1.5 hours The product was extracted into dichloromethane (3×200 ml) the combined extracts were washed with water (2×200 ml) dried (Na2SO4) the solvent removed in vacuo

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 2-methoxyphenylacetone (5 g, 30.5 mmol) in N,N-dimethylformamide dimethyl acetal (8.7 ml, 73.1 mmol) was stirred at 80° C. for 4 hours. The mixture was concentrated under vacuum. The resulting residue was dissolved in dichloromethane (40 ml), cooled to 0° C. and treated with a solution of boron tribromide (5 ml, 52.9 mmol) in dichloromethane (10 ml). After stirring at 0° C. for 1 hour, additional boron tribromide (5 ml, 52.9 mmol) was added. The mixture was stirred at 0° C. for 10 more minutes and was poured into a mixture of ice and saturated aqueous sodium bicarbonate. The resulting mixture was extracted with dichloromethane three times. The combined organic extracts were washed with water once and dried over anhydrous sodium sulfate to give 3-acetylbenzofuran (4.7 g, 96%, 94.5% AUC HPLC): 1H NMR (300 MHz, CDCl3) δ 8.16-8.19 (m, 2H), 7.44-7.48 (m, 1H), 7.29-7.32 (m, 2H), 2.50 (s, 3H). The mixture was concentrated under vacuum The resulting residue was dissolved in dichloromethane (40 ml) The mixture was stirred at 0° C. for 10 more minutes The resulting mixture was extracted with dichloromethane three times The combined organic extracts were washed with water once dried over anhydrous sodium sulfate

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 1-benzofuran-3-yl-2-bromo-ethanone (Intermediate I1) (commercially available from Maybridge) (2.1 g, 8.8 mmol) in toluene at reflux was treated with tributyltin hydride (2.9 mL, 10.6 mmol) and 2,2′-azobisisobutyronitrile (AIBN, catalyst) for 2 h. The mixture was cooled to rt and concentrated onto silica gel under reduced pressure. The product was eluted from a column of silica gel with 5% EtOAc: hexane to give 1-benzofuran-3-yl-ethanone (Intermediate I2) as an oil, 1.45 g (99%). concentrated onto silica gel under reduced pressure The product was eluted from a column of silica gel with 5% EtOAc

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 2-methoxyphenylacetone (5 g, 30.5 mmol) in N,N-dimethylformamide dimethyl acetal (8.7 ml, 73.1 mmol) was stirred at 80° C. for 4 hours. The mixture was concentrated under vacuum. The resulting residue was dissolved in dichloromethane (40 ml), cooled to 0° C. and treated with a solution of boron tribromide (5 ml, 52.9 mmol) in dichloromethane (10 ml). After stirring at 0° C. for 1 hour, additional boron tribromide (5 ml, 52.9 mmol) was added. The mixture was stirred at 0° C. for 10 more minutes and was poured into a mixture of ice and saturated aqueous sodium bicarbonate. The resulting mixture was extracted with dichloromethane three times. The combined organic extracts were washed with water once and dried over anhydrous sodium sulfate to give 3-acetylbenzofuran (4.7 g, 96%, 94.5% AUC HPLC): 1H NMR (300 MHz, CDCl3) δ 8.16-8.19 (m, 2H), 7.44-7.48 (m, 1H), 7.29-7.32 (m, 2H), 2.50 (s, 3H). The mixture was concentrated under vacuum The resulting residue was dissolved in dichloromethane (40 ml) The mixture was stirred at 0° C. for 10 more minutes The resulting mixture was extracted with dichloromethane three times The combined organic extracts were washed with water once dried over anhydrous sodium sulfate

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 1-(2-methoxyphenyl)propan-2-one (77.2 g) and dimethylformamide dimethyl acetal (137.5 g) was stirred at 80° C. under nitrogen for 4 hours, then concentrated in vacuo to leave a viscous oil. The oil was dissolved in dichloromethane (620 ml) then the stirred solution was cooled to 0° C. Boron tribromide (1M solution in dichloromethane, 800 ml) was added dropwise over 1.75 hours at 0°-5° C., then the mixture was stirred at 0°-5° C. for a further 1.5 hours and poured onto an excess of ice and saturated aqueous sodium hydrogen carbonate solution. Solid sodium hydrogen carbonate was added in portions with occasional stirring until effervescence ceased. The product was extracted into dichloromethane (3×600 ml) then the combined extracts were washed with water (2×600 ml), dried (Na2SO4), and the solvent removed in vacuo to leave 3-acetylbenzo[b]furan as a brown oil (78.9 g). concentrated in vacuo to leave a viscous oil the stirred solution was cooled to 0° C the mixture was stirred at 0°-5° C. for a further 1.5 hours with occasional stirring until effervescence The product was extracted into dichloromethane (3×600 ml) the combined extracts were washed with water (2×600 ml) dried (Na2SO4) the solvent removed in vacuo

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of phenyltrimethylammonium tribromide (2.47 g) in tetrahydrofuran (20 ml) was added dropwise at ambient temperature under nitrogen over 5 minutes to a stirred solution of 3-acetylbenzo[b]furan (1 g) in tetrahydrofuran (20 ml), then the mixture was stirred at ambient temperature for a further 1.5 hours, filtered, and the solvent removed in vacuo. The residue was triturated with ether, and the resulting solid was collected by filtration and dried in vacuo at ambient temperature to give 3-(2-bromoacetyl)benzo[b]furan as an off-white solid (0.25 g). filtered the solvent removed in vacuo The residue was triturated with ether the resulting solid was collected by filtration dried in vacuo at ambient temperature

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of phenyltrimethylammonium tribromide (2.47 g) in tetrahydrofuran (20 ml) was added dropwise at ambient temperature under nitrogen over 5 minutes to a stirred solution of 3-acetylbenzo[b]furan (1 g) in tetrahydrofuran (20 ml), then the mixture was stirred at ambient temperature for a further 1.5 hours, filtered, and the solvent removed in vacuo. The residue was triturated with ether, and the resulting solid was collected by filtration and dried in vacuo at ambient temperature to give 3-(2-bromoacetyl)benzo[b]furan as an off-white solid (0.25 g). filtered the solvent removed in vacuo The residue was triturated with ether the resulting solid was collected by filtration dried in vacuo at ambient temperature

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 1-(2-methoxyphenyl)propan-2-one (10 g) and dimethylformamide dimethyl acetal (17.8 g) was stirred at 80° C, under nitrogen for 4 hours, then concentrated in vacuo to leave a viscous oil. The oil was disolved in dichloromethane (80 ml), and the solution was stirred and cooled in an ice-bath while boron tribromide (1M solution in dichloromethane; 104 ml) was added dropwise over 15 minutes. When the addition was complete, the mixture was stirred, with ice-cooling, for a further 1.5 hours, then it was poured into an excess of ice and saturated aqueous sodium hydrogen carbonate solution. The product was extracted into dichloromethane (3×200 ml) and the combined extracts were washed with water (2×200 ml), dried (Na2SO4), and the solvent removed in vacuo to leave 3-acetylbenzo[b]furan as a dark red oil (4.25 g). concentrated in vacuo to leave a viscous oil the solution was stirred was added dropwise over 15 minutes When the addition the mixture was stirred, with ice- cooling, for a further 1.5 hours The product was extracted into dichloromethane (3×200 ml) the combined extracts were washed with water (2×200 ml) dried (Na2SO4) the solvent removed in vacuo

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 1-(2-methoxyphenyl)propan-2-one (10 g) and dimethylformamide dimethyl acetal (17.8 g) was stirred at 80° C, under nitrogen for 4 hours, then concentrated in vacuo to leave a viscous oil. The oil was disolved in dichloromethane (80 ml), and the solution was stirred and cooled in an ice-bath while boron tribromide (1M solution in dichloromethane; 104 ml) was added dropwise over 15 minutes. When the addition was complete, the mixture was stirred, with ice-cooling, for a further 1.5 hours, then it was poured into an excess of ice and saturated aqueous sodium hydrogen carbonate solution. The product was extracted into dichloromethane (3×200 ml) and the combined extracts were washed with water (2×200 ml), dried (Na2SO4), and the solvent removed in vacuo to leave 3-acetylbenzo[b]furan as a dark red oil (4.25 g). concentrated in vacuo to leave a viscous oil the solution was stirred was added dropwise over 15 minutes When the addition the mixture was stirred, with ice- cooling, for a further 1.5 hours The product was extracted into dichloromethane (3×200 ml) the combined extracts were washed with water (2×200 ml) dried (Na2SO4) the solvent removed in vacuo