4,5-difluoro-2-methoxybenzaldehyde

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

実験手順: Following the procedure used to prepare 1-(5-fluoro-2-methoxy-phenyl)-3-phenyl-prop-2-yn-1-ol, 2-methoxy-4,5-difluorobenzaldehyde was reacted to give the title compound as a colourless oil (531 mg, 97%). LCMS (Method B): RT=3.90 min, [M−H2O+H]+=257. was reacted

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

実験手順: A solution of 5.8 g (33.7 mmol) of 4,5-difluoro-2-methoxybenzaldehyde in 400 ml of anhydrous dichloromethane was treated dropwise at -70° while stirring over a period of 10 minutes with 37 ml (37 mmol) of a 1 M boron tribromide solution in dichloromethane. Subsequently, the mixture was stirred at room temperature for 16 hours, poured on to 400 ml of ice-water and the phases were separated. The aqueous phase was extracted once with 400 ml of dichloromethane and the combined organic phases were washed once with 200 ml of saturated sodium chloride solution, dried over magnesium sulphate and concentrated in a vacuum. The crude product obtained was purified by column chromatography on silica gel (hexane/ethyl acetate 4:1). There were obtained 5.05 g (94%) of 4,5-difluoro-2-hydroxybenzaldehyde as a white solid with m.p. 64°. the phases were separated The aqueous phase was extracted once with 400 ml of dichloromethane the combined organic phases were washed once with 200 ml of saturated sodium chloride solution dried over magnesium sulphate concentrated in a vacuum The crude product obtained was purified by column chromatography on silica gel (hexane/ethyl acetate 4:1)

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

実験手順: 7.29 ml (66.3 mmol) of titanium tetrachloride were added while stirring to a solution, cooled to 0°, of 5.73 g (39.8 mmol) of 3,4-difluoroanisole in 30 ml of anhydrous dichloromethane. Subsequently, the mixture was treated dropwise over 10 minutes with 3.51 ml (39.6 mmol) of 1,1-dichloromethyl methyl ketone and stirred at room temperature for one hour. The mixture was poured into 100 ml of ice-water, extracted twice with 150 ml of dichloromethane each time and the combined organic phases were washed once with 100 ml of water and once with 100 ml of saturated sodium chloride solution. After drying over magnesium sulfate concentration was carried out in a vacuum. The crude product obtained was purified by column chromatography on silica gel (hexane/ethyl acetate 4:1). There were obtained 5.8 g (84%) of 4,5-difluoro-2-methoxybenzaldehyde as a white solid with m.p. 74°. stirred at room temperature for one hour extracted twice with 150 ml of dichloromethane each time the combined organic phases were washed once with 100 ml of water and once with 100 ml of saturated sodium chloride solution After drying over magnesium sulfate concentration The crude product obtained was purified by column chromatography on silica gel (hexane/ethyl acetate 4:1)

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

実験手順: 7.29 ml (66.3 mmol) of titanium tetrachloride were added while stirring to a solution, cooled to 0°, of 5.73 g (39.8 mmol) of 3,4-difluoroanisole in 30 ml of anhydrous dichloromethane. Subsequently, the mixture was treated dropwise over 10 minutes with 3.51 ml (39.6 mmol) of 1,1-dichloromethyl methyl ketone and stirred at room temperature for one hour. The mixture was poured into 100 ml of ice-water, extracted twice with 150 ml of dichloromethane each time and the combined organic phases were washed once with 100 ml of water and once with 100 ml of saturated sodium chloride solution. After drying over magnesium sulfate concentration was carried out in a vacuum. The crude product obtained was purified by column chromatography on silica gel (hexane/ethyl acetate 4:1). There were obtained 5.8 g (84%) of 4,5-difluoro-2-methoxybenzaldehyde as a white solid with m.p. 74°. stirred at room temperature for one hour extracted twice with 150 ml of dichloromethane each time the combined organic phases were washed once with 100 ml of water and once with 100 ml of saturated sodium chloride solution After drying over magnesium sulfate concentration The crude product obtained was purified by column chromatography on silica gel (hexane/ethyl acetate 4:1)

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

実験手順: Following the procedure used to prepare 1-(5-fluoro-2-methoxy-phenyl)-3-phenyl-prop-2-yn-1-ol, 2-methoxy-4,5-difluorobenzaldehyde was reacted to give the title compound as a colourless oil (531 mg, 97%). LCMS (Method B): RT=3.90 min, [M−H2O+H]+=257. was reacted

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

実験手順: A solution of 5.8 g (33.7 mmol) of 4,5-difluoro-2-methoxybenzaldehyde in 400 ml of anhydrous dichloromethane was treated dropwise at -70° while stirring over a period of 10 minutes with 37 ml (37 mmol) of a 1 M boron tribromide solution in dichloromethane. Subsequently, the mixture was stirred at room temperature for 16 hours, poured on to 400 ml of ice-water and the phases were separated. The aqueous phase was extracted once with 400 ml of dichloromethane and the combined organic phases were washed once with 200 ml of saturated sodium chloride solution, dried over magnesium sulphate and concentrated in a vacuum. The crude product obtained was purified by column chromatography on silica gel (hexane/ethyl acetate 4:1). There were obtained 5.05 g (94%) of 4,5-difluoro-2-hydroxybenzaldehyde as a white solid with m.p. 64°. the phases were separated The aqueous phase was extracted once with 400 ml of dichloromethane the combined organic phases were washed once with 200 ml of saturated sodium chloride solution dried over magnesium sulphate concentrated in a vacuum The crude product obtained was purified by column chromatography on silica gel (hexane/ethyl acetate 4:1)

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

実験手順: 7.29 ml (66.3 mmol) of titanium tetrachloride were added while stirring to a solution, cooled to 0°, of 5.73 g (39.8 mmol) of 3,4-difluoroanisole in 30 ml of anhydrous dichloromethane. Subsequently, the mixture was treated dropwise over 10 minutes with 3.51 ml (39.6 mmol) of 1,1-dichloromethyl methyl ketone and stirred at room temperature for one hour. The mixture was poured into 100 ml of ice-water, extracted twice with 150 ml of dichloromethane each time and the combined organic phases were washed once with 100 ml of water and once with 100 ml of saturated sodium chloride solution. After drying over magnesium sulfate concentration was carried out in a vacuum. The crude product obtained was purified by column chromatography on silica gel (hexane/ethyl acetate 4:1). There were obtained 5.8 g (84%) of 4,5-difluoro-2-methoxybenzaldehyde as a white solid with m.p. 74°. stirred at room temperature for one hour extracted twice with 150 ml of dichloromethane each time the combined organic phases were washed once with 100 ml of water and once with 100 ml of saturated sodium chloride solution After drying over magnesium sulfate concentration The crude product obtained was purified by column chromatography on silica gel (hexane/ethyl acetate 4:1)