3-bromo-2-hydroxy-5-methoxybenzaldehyde

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-Bromo-2-hydroxy-5-methoxybenzaldehyde (1.5 g, 6.49 mmol), 2-chloro-N,N-dimethylacetamide (0.73 mL, 7.14 mmol) and potassium carbonate (1.8 g, 13.0 mmol) were heated to reflux in dimethylformamide (15 mL) for 2 h. The solvent was removed in vacuo and the residue was taken up in ethyl acetate and washed with water and brine. The organic phase was dried over MgSO4, filtered and then concentrated by rotary evaporation. The crude product was purified by flash chromatography (SiO2; heptane/EtOAc, gradient 0-100%). Yield: 1.5 g (77%). The solvent was removed in vacuo washed with water and brine The organic phase was dried over MgSO4 filtered concentrated by rotary evaporation The crude product was purified by flash chromatography (SiO2; heptane/EtOAc, gradient 0-100%)

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

実験手順: To 2-hydroxy-5-methoxybenzaldehyde (4.1 mL, 32.86 mmol) in acetic acid (150 mL) were added sodium acetate (4.0 g, 49.3 mmol) and bromine (2.2 mL, 42.7 mmol) and the mixture was stirred at rt for 2 h. Aqueous sodium thiosulfate was added and the mixture was concentrated by rotary evaporation. The solid was dissolved in dichloromethane and washed with water. The organic phase was separated, dried over MgSO4, filtered and the solvent removed by rotary evaporation. The solid residue was recrystallized from ethanol to yield 3-bromo-2-hydroxy-5-methoxybenzaldehyde (4.55 g, 60%). the mixture was concentrated by rotary evaporation The solid was dissolved in dichloromethane washed with water The organic phase was separated dried over MgSO4 filtered the solvent removed by rotary evaporation The solid residue was recrystallized from ethanol

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

実験手順: 3-Bromo-2-hydroxy-5-methoxybenzaldehyde (1.5 g, 6.49 mmol), 2-chloro-N,N-dimethylacetamide (0.73 mL, 7.14 mmol) and potassium carbonate (1.8 g, 13.0 mmol) were heated to reflux in dimethylformamide (15 mL) for 2 h. The solvent was removed in vacuo and the residue was taken up in ethyl acetate and washed with water and brine. The organic phase was dried over MgSO4, filtered and then concentrated by rotary evaporation. The crude product was purified by flash chromatography (SiO2; heptane/EtOAc, gradient 0-100%). The solvent was removed in vacuo washed with water and brine The organic phase was dried over MgSO4 filtered concentrated by rotary evaporation The crude product was purified by flash chromatography (SiO2; heptane/EtOAc, gradient 0-100%)

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

実験手順: To 2-hydroxy-5-methoxybenzaldehyde (4.1 mL, 32.86 mmol) in acetic acid (150 mL) were added sodium acetate (4.0 g, 49.3 mmol) and bromine (2.2 mL, 42.7 mmol) and the mixture was stirred at rt for 2 h. Aqueous sodium thiosulfate was added and the mixture was concentrated by rotary evaporation. The solid was dissolved in dichloromethane and washed with water. The organic phase was separated, dried over MgSO4, filtered and the solvent removed by rotary evaporation. The solid residue was recrystallized from ethanol to yield 3-bromo-2-hydroxy-5-methoxybenzaldehyde (4.55 g, 60%). the mixture was concentrated by rotary evaporation The solid was dissolved in dichloromethane washed with water The organic phase was separated dried over MgSO4 filtered the solvent removed by rotary evaporation The solid residue was recrystallized from ethanol

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

実験手順: To 2-hydroxy-5-methoxybenzaldehyde (4.1 mL, 32.86 mmol) in acetic acid (150 mL) were added sodium acetate (4.0 g, 49.3 mmol) and bromine (2.2 mL, 42.7 mmol) and the mixture was stirred at rt for 2 h. Aqueous sodium thiosulfate was added and the mixture was concentrated by rotary evaporation. The solid was dissolved in dichloromethane and washed with water. The organic phase was separated, dried over MgSO4, filtered and the solvent removed by rotary evaporation. The solid residue was recrystallized from ethanol to yield 3-bromo-2-hydroxy-5-methoxybenzaldehyde (4.55 g, 60%). the mixture was concentrated by rotary evaporation The solid was dissolved in dichloromethane washed with water The organic phase was separated dried over MgSO4 filtered the solvent removed by rotary evaporation The solid residue was recrystallized from ethanol

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

実験手順: 3-Bromo-2-hydroxy-5-methoxybenzaldehyde (1.5 g, 6.49 mmol), 2-chloro-N,N-dimethylacetamide (0.73 mL, 7.14 mmol) and potassium carbonate (1.8 g, 13.0 mmol) were heated to reflux in dimethylformamide (15 mL) for 2 h. The solvent was removed in vacuo and the residue was taken up in ethyl acetate and washed with water and brine. The organic phase was dried over MgSO4, filtered and then concentrated by rotary evaporation. The crude product was purified by flash chromatography (SiO2; heptane/EtOAc, gradient 0-100%). Yield: 1.5 g (77%). The solvent was removed in vacuo washed with water and brine The organic phase was dried over MgSO4 filtered concentrated by rotary evaporation The crude product was purified by flash chromatography (SiO2; heptane/EtOAc, gradient 0-100%)

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

実験手順: 3-Bromo-2-hydroxy-5-methoxybenzaldehyde (1.5 g, 6.49 mmol), 2-chloro-N,N-dimethylacetamide (0.73 mL, 7.14 mmol) and potassium carbonate (1.8 g, 13.0 mmol) were heated to reflux in dimethylformamide (15 mL) for 2 h. The solvent was removed in vacuo and the residue was taken up in ethyl acetate and washed with water and brine. The organic phase was dried over MgSO4, filtered and then concentrated by rotary evaporation. The crude product was purified by flash chromatography (SiO2; heptane/EtOAc, gradient 0-100%). Yield: 1.5 g (77%). The solvent was removed in vacuo washed with water and brine The organic phase was dried over MgSO4 filtered concentrated by rotary evaporation The crude product was purified by flash chromatography (SiO2; heptane/EtOAc, gradient 0-100%)

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

実験手順: To 2-hydroxy-5-methoxybenzaldehyde (4.1 mL, 32.86 mmol) in acetic acid (150 mL) were added sodium acetate (4.0 g, 49.3 mmol) and bromine (2.2 mL, 42.7 mmol) and the mixture was stirred at rt for 2 h. Aqueous sodium thiosulfate was added and the mixture was concentrated by rotary evaporation. The solid was dissolved in dichloromethane and washed with water. The organic phase was separated, dried over MgSO4, filtered and the solvent removed by rotary evaporation. The solid residue was recrystallized from ethanol to yield 3-bromo-2-hydroxy-5-methoxybenzaldehyde (4.55 g, 60%). the mixture was concentrated by rotary evaporation The solid was dissolved in dichloromethane washed with water The organic phase was separated dried over MgSO4 filtered the solvent removed by rotary evaporation The solid residue was recrystallized from ethanol

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

実験手順: To 2-hydroxy-5-methoxybenzaldehyde (4.1 mL, 32.86 mmol) in acetic acid (150 mL) were added sodium acetate (4.0 g, 49.3 mmol) and bromine (2.2 mL, 42.7 mmol) and the mixture was stirred at rt for 2 h. Aqueous sodium thiosulfate was added and the mixture was concentrated by rotary evaporation. The solid was dissolved in dichloromethane and washed with water. The organic phase was separated, dried over MgSO4, filtered and the solvent removed by rotary evaporation. The solid residue was recrystallized from ethanol to yield 3-bromo-2-hydroxy-5-methoxybenzaldehyde (4.55 g, 60%). the mixture was concentrated by rotary evaporation The solid was dissolved in dichloromethane washed with water The organic phase was separated dried over MgSO4 filtered the solvent removed by rotary evaporation The solid residue was recrystallized from ethanol

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

実験手順: To a solution containing 3-Bromo-2-hydroxy-5-methoxy-benzaldehyde (94.7 g, 0.410 mol) and dimethyl bromomalonate (103 g, 0.492 mol) in toluene (1.2 L) was added freshly powdered potassium carbonate (85 g, 0.615 mol) and tetra-n-butylammonium bromide (13.2 g, 0.041 mol). The reaction was heated at reflux under a Dean-Stark trap for 48 h. The reaction was concentrated and the residue dissolved with dichloromethane (−0.5 L) and filtered through Celite, washing with dichloromethane (˜0.5 L). The filtrate was washed with 1 L of 1M sodium hydroxide and water (2×1 L). The organic phase was then passed through a 400 g pad of silica gel washing with dichloromethane (˜1 L) and the filtrate was concentrated to give the desired benzofuran (64 g, 56%) as an orange solid, mp 107–111° C. 1H NMR δ (CDCl3) 7.50 (s, 1H), 7.23 (d, 1H), 7.03 (d, 1H), 3.98 (s, 3H), 3.82 (s, 3H). The reaction was heated at reflux under a Dean-Stark trap for 48 h The reaction was concentrated the residue dissolved with dichloromethane (−0.5 L) filtered through Celite washing with dichloromethane (˜0.5 L) The filtrate was washed with 1 L of 1M sodium hydroxide and water (2×1 L) the filtrate was concentrated

反応条件: temp:0.00; pressure:0.00; stir: