5-bromo-2-methyl-1-benzofuran-3-one

Conditions: temp:75.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A suspension of acetic acid 5-bromo-2-methyl-benzofuran-3-yl ester (18.9 g, 70.4 mmol) in methanol (232 mL) and a 1 M aqueous HCl solution (44 mL) is heated under reflux (75° C.) for 7 h. After cooling to room temperature the reaction mixture is concentrated by rotary evaporation. The residue is diluted with water and extracted three times with diethyl ether. The combined organic layers are washed with water, brine, dried over Na2SO4, filtered and concentrated at reduced pressure to afford the title compound as a yellow oil (14.7 g, 64.7 mmol, 92%). MS (ES+): 227 (M(C9H779BrO2)+H)+. After cooling to room temperature the reaction mixture is concentrated by rotary evaporation The residue is diluted with water extracted three times with diethyl ether The combined organic layers are washed with water, brine dried over Na2SO4 filtered concentrated at reduced pressure

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 5-bromo-2-methyl-benzofuran-3-one (6.8 g, 29.9 mmol) and (triphenyl-phosphanylidene)-acetic acid ethyl ester (17.4 g, 44.9 mmol) in anhydrous toluene is heated for 40 h at 120° C. under an argon atmosphere. After cooling to room temperature the volatiles are removed by rotary evaporation. The residue is purified by flash column chromatography (silica gel, gradient of cyclohexane/EtOAc 100:0 to 90:10) to afford a mixture of two regioisomeric products. The product mixture (7.1 g, 31.3 mmol) is dissolved in a 1.25 M solution of HCl in ethanol and heated at reflux for 1 h. After cooling to room temperature the solvent is removed by rotary evaporation to yield the title compound as a pale yellow oil (6.9 g, 23.2 mmol, 78%). 1H NMR (400 MHz, CDCl3, 298 K): δ=7.59 (d, J=2.0 Hz, 1H), 7.31-7.22 (m, 2H), 4.15 (q, J=7.1 Hz, 2H), 3.54 (s, 2H), 2.42 (s, 3H), 1.25 (t, J=7.1 Hz, 3H). MS (ES+): 297 (M(C13H1379BrO3)+H)+. After cooling to room temperature the volatiles are removed by rotary evaporation The residue is purified by flash column chromatography (silica gel, gradient of cyclohexane/EtOAc 100:0 to 90:10) to afford a mixture of two regioisomeric products heated at reflux for 1 h After cooling to room temperature the solvent is removed by rotary evaporation

Conditions: temp:75.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A suspension of acetic acid 5-bromo-2-methyl-benzofuran-3-yl ester (18.9 g, 70.4 mmol) in methanol (232 mL) and a 1 M aqueous HCl solution (44 mL) is heated under reflux (75° C.) for 7 h. After cooling to room temperature the reaction mixture is concentrated by rotary evaporation. The residue is diluted with water and extracted three times with diethyl ether. The combined organic layers are washed with water, brine, dried over Na2SO4, filtered and concentrated at reduced pressure to afford the title compound as a yellow oil (14.7 g, 64.7 mmol, 92%). MS (ES+): 227 (M(C9H779BrO2)+H)+. After cooling to room temperature the reaction mixture is concentrated by rotary evaporation The residue is diluted with water extracted three times with diethyl ether The combined organic layers are washed with water, brine dried over Na2SO4 filtered concentrated at reduced pressure

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 5-bromo-2-methyl-benzofuran-3-one (6.8 g, 29.9 mmol) and (triphenyl-phosphanylidene)-acetic acid ethyl ester (17.4 g, 44.9 mmol) in anhydrous toluene is heated for 40 h at 120° C. under an argon atmosphere. After cooling to room temperature the volatiles are removed by rotary evaporation. The residue is purified by flash column chromatography (silica gel, gradient of cyclohexane/EtOAc 100:0 to 90:10) to afford a mixture of two regioisomeric products. The product mixture (7.1 g, 31.3 mmol) is dissolved in a 1.25 M solution of HCl in ethanol and heated at reflux for 1 h. After cooling to room temperature the solvent is removed by rotary evaporation to yield the title compound as a pale yellow oil (6.9 g, 23.2 mmol, 78%). 1H NMR (400 MHz, CDCl3, 298 K): δ=7.59 (d, J=2.0 Hz, 1H), 7.31-7.22 (m, 2H), 4.15 (q, J=7.1 Hz, 2H), 3.54 (s, 2H), 2.42 (s, 3H), 1.25 (t, J=7.1 Hz, 3H). MS (ES+): 297 (M(C13H1379BrO3)+H)+. After cooling to room temperature the volatiles are removed by rotary evaporation The residue is purified by flash column chromatography (silica gel, gradient of cyclohexane/EtOAc 100:0 to 90:10) to afford a mixture of two regioisomeric products heated at reflux for 1 h After cooling to room temperature the solvent is removed by rotary evaporation

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 5-bromo-2-methyl-benzofuran-3-one (6.8 g, 29.9 mmol) and (triphenyl-phosphanylidene)-acetic acid ethyl ester (17.4 g, 44.9 mmol) in anhydrous toluene is heated for 40 h at 120° C. under an argon atmosphere. After cooling to room temperature the volatiles are removed by rotary evaporation. The residue is purified by flash column chromatography (silica gel, gradient of cyclohexane/EtOAc 100:0 to 90:10) to afford a mixture of two regioisomeric products. The product mixture (7.1 g, 31.3 mmol) is dissolved in a 1.25 M solution of HCl in ethanol and heated at reflux for 1 h. After cooling to room temperature the solvent is removed by rotary evaporation to yield the title compound as a pale yellow oil (6.9 g, 23.2 mmol, 78%). 1H NMR (400 MHz, CDCl3, 298 K): δ=7.59 (d, J=2.0 Hz, 1H), 7.31-7.22 (m, 2H), 4.15 (q, J=7.1 Hz, 2H), 3.54 (s, 2H), 2.42 (s, 3H), 1.25 (t, J=7.1 Hz, 3H). MS (ES+): 297 (M(C13H1379BrO3)+H)+. After cooling to room temperature the volatiles are removed by rotary evaporation The residue is purified by flash column chromatography (silica gel, gradient of cyclohexane/EtOAc 100:0 to 90:10) to afford a mixture of two regioisomeric products heated at reflux for 1 h After cooling to room temperature the solvent is removed by rotary evaporation

Conditions: temp:75.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A suspension of acetic acid 5-bromo-2-methyl-benzofuran-3-yl ester (18.9 g, 70.4 mmol) in methanol (232 mL) and a I M aqueous HCl solution (44 mL) is heated under reflux (75° C.) for 7 h. After cooling to room temperature the reaction mixture is concentrated by rotary evaporation. The residue is diluted with water and extracted three times with diethyl ether. The combined organic layers are washed with water, brine, dried over Na2SO4, filtered and concentrated at reduced pressure to afford the title compound as a yellow oil (14.7 g, 64.7 mmol, 92%). MS (ES+): 227 (M(C9H779BrO2)+H)+. After cooling to room temperature the reaction mixture is concentrated by rotary evaporation The residue is diluted with water extracted three times with diethyl ether The combined organic layers are washed with water, brine dried over Na2SO4 filtered concentrated at reduced pressure

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 5-bromo-2-methyl-benzofuran-3-one (6.8 g, 29.9 mmol) and (triphenyl-phosphanylidene)-acetic acid ethyl ester (17.4 g, 44.9 mmol) in anhydrous toluene is heated for 40 h at 120° C. under an argon atmosphere. After cooling to room temperature the volatiles are removed by rotary evaporation. The residue is purified by flash column chromatography (silica gel, gradient of cyclohexane/EtOAc 100:0 to 90:10) to afford a mixture of two regioisomeric products. The product mixture (7.1 g, 31.3 mmol) is dissolved in a 1.25 M solution of HCl in ethanol and heated at reflux for 1 h. After cooling to room temperature the solvent is removed by rotary evaporation to yield the title compound as a pale yellow oil (6.9 g, 23.2 mmol, 78%). 1H NMR (400 MHz, CDCl3, 298 K): δ=7.59 (d, J=2.0 Hz, 1H), 7.31-7.22 (m, 2H), 4.15 (q, J=7.1 Hz, 2H), 3.54 (s, 2H), 2.42 (s, 3H), 1.25 (t, J=7.1 Hz, 3H). MS (ES+): 297 (M(C13H1379BrO3)+H)+. After cooling to room temperature the volatiles are removed by rotary evaporation The residue is purified by flash column chromatography (silica gel, gradient of cyclohexane/EtOAc 100:0 to 90:10) to afford a mixture of two regioisomeric products heated at reflux for 1 h After cooling to room temperature the solvent is removed by rotary evaporation

Conditions: temp:75.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A suspension of acetic acid 5-bromo-2-methyl-benzofuran-3-yl ester (18.9 g, 70.4 mmol) in methanol (232 mL) and a I M aqueous HCl solution (44 mL) is heated under reflux (75° C.) for 7 h. After cooling to room temperature the reaction mixture is concentrated by rotary evaporation. The residue is diluted with water and extracted three times with diethyl ether. The combined organic layers are washed with water, brine, dried over Na2SO4, filtered and concentrated at reduced pressure to afford the title compound as a yellow oil (14.7 g, 64.7 mmol, 92%). MS (ES+): 227 (M(C9H779BrO2)+H)+. After cooling to room temperature the reaction mixture is concentrated by rotary evaporation The residue is diluted with water extracted three times with diethyl ether The combined organic layers are washed with water, brine dried over Na2SO4 filtered concentrated at reduced pressure

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 5-bromo-2-methyl-benzofuran-3-one (6.8 g, 29.9 mmol) and (triphenyl-phosphanylidene)-acetic acid ethyl ester (17.4 g, 44.9 mmol) in anhydrous toluene is heated for 40 h at 120° C. under an argon atmosphere. After cooling to room temperature the volatiles are removed by rotary evaporation. The residue is purified by flash column chromatography (silica gel, gradient of cyclohexane/EtOAc 100:0 to 90:10) to afford a mixture of two regioisomeric products. The product mixture (7.1 g, 31.3 mmol) is dissolved in a 1.25 M solution of HCl in ethanol and heated at reflux for 1 h. After cooling to room temperature the solvent is removed by rotary evaporation to yield the title compound as a pale yellow oil (6.9 g, 23.2 mmol, 78%). 1H NMR (400 MHz, CDCl3, 298 K): δ=7.59 (d, J=2.0 Hz, 1H), 7.31-7.22 (m, 2H), 4.15 (q, J=7.1 Hz, 2H), 3.54 (s, 2H), 2.42 (s, 3H), 1.25 (t, J=7.1 Hz, 3H). MS (ES+): 297 (M(C13H1379BrO3)+H)+. After cooling to room temperature the volatiles are removed by rotary evaporation The residue is purified by flash column chromatography (silica gel, gradient of cyclohexane/EtOAc 100:0 to 90:10) to afford a mixture of two regioisomeric products heated at reflux for 1 h After cooling to room temperature the solvent is removed by rotary evaporation

Conditions: temp:75.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A suspension of acetic acid 5-bromo-2-methyl-benzofuran-3-yl ester (18.9 g, 70.4 mmol) in methanol (232 mL) and a 1 M aqueous HCl solution (44 mL) is heated under reflux (75° C.) for 7 h. After cooling to room temperature the reaction mixture is concentrated by rotary evaporation. The residue is diluted with water and extracted three times with diethyl ether. The combined organic layers are washed with water, brine, dried over Na2SO4, filtered and concentrated at reduced pressure to afford the title compound as a yellow oil (14.7 g, 64.7 mmol, 92%). MS (ES+): 227 (M(C9H779BrO2)+H)+. After cooling to room temperature the reaction mixture is concentrated by rotary evaporation The residue is diluted with water extracted three times with diethyl ether The combined organic layers are washed with water, brine dried over Na2SO4 filtered concentrated at reduced pressure

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 5-bromo-2-methyl-benzofuran-3-one (6.8 g, 29.9 mmol) and (triphenyl-phosphanylidene)-acetic acid ethyl ester (17.4 g, 44.9 mmol) in anhydrous toluene is heated for 40 h at 120° C. under an argon atmosphere. After cooling to room temperature the volatiles are removed by rotary evaporation. The residue is purified by flash column chromatography (silica gel, gradient of cyclohexane/EtOAc 100:0 to 90:10) to afford a mixture of two regioisomeric products. The product mixture (7.1 g, 31.3 mmol) is dissolved in a 1.25 M solution of HCl in ethanol and heated at reflux for 1 h. After cooling to room temperature the solvent is removed by rotary evaporation to yield the title compound as a pale yellow oil (6.9 g, 23.2 mmol, 78%). 1H NMR (400 MHz, CDCl3, 298 K): δ=7.59 (d, J=2.0 Hz, 1H), 7.31-7.22 (m, 2H), 4.15 (q, J=7.1 Hz, 2H), 3.54 (s, 2H), 2.42 (s, 3H), 1.25 (t, J=7.1 Hz, 3H). MS (ES+): 297 (M(C13H1379BrO3)+H)+. After cooling to room temperature the volatiles are removed by rotary evaporation The residue is purified by flash column chromatography (silica gel, gradient of cyclohexane/EtOAc 100:0 to 90:10) to afford a mixture of two regioisomeric products heated at reflux for 1 h After cooling to room temperature the solvent is removed by rotary evaporation

Conditions: temp:75.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A suspension of acetic acid 5-bromo-2-methyl-benzofuran-3-yl ester (18.9 g, 70.4 mmol) in methanol (232 mL) and a I M aqueous HCl solution (44 mL) is heated under reflux (75° C.) for 7 h. After cooling to room temperature the reaction mixture is concentrated by rotary evaporation. The residue is diluted with water and extracted three times with diethyl ether. The combined organic layers are washed with water, brine, dried over Na2SO4, filtered and concentrated at reduced pressure to afford the title compound as a yellow oil (14.7 g, 64.7 mmol, 92%). MS (ES+): 227 (M(C9H779BrO2)+H)+. After cooling to room temperature the reaction mixture is concentrated by rotary evaporation The residue is diluted with water extracted three times with diethyl ether The combined organic layers are washed with water, brine dried over Na2SO4 filtered concentrated at reduced pressure