4-fluoro-2,3-dihydroisoindol-1-one

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

実験手順: At 0° C., 645 mg (4.27 mmol) of 4-fluoro-2,3-dihydro-1H-isoindol-1-one were added to 170.7 mg (4.27 mmol, 60% pure) of sodium hydride in 4 ml of DMF. The mixture was stirred for 30 min, and 2.11 g (5.98 mmol) of ethyl 2-[4-(bromomethyl)phenyl]-4,4,4-trifluoro-3-methylbutanoate were then added at 0° C. The reaction mixture was stirred for a further 2 h, and water and ethyl acetate were then added. The organic phase was washed with saturated sodium chloride solution and dried over magnesium sulfate. The crude product was purified by chromatography on silica gel (mobile phase cyclohexane/ethyl acetate 40:1 to 3:1). This gave 856 mg (33.9% of theory) of the target compound. The reaction mixture was stirred for a further 2 h The organic phase was washed with saturated sodium chloride solution dried over magnesium sulfate The crude product was purified by chromatography on silica gel (mobile phase cyclohexane/ethyl acetate 40:1 to 3:1)

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

実験手順: At 0° C., 280 mg (1.85 mmol) of 4-fluoro-2,3-dihydro-1H-isoindol-1-one were added to a suspension of 96.3 mg (2.41 mmol, 60% pure) of sodium hydride in 1 ml of DMF. The mixture was stirred for 30 min, and 654.5 mg (1.85 mmol) of tert-butyl(+/−)-[4-(bromomethyl)phenyl](cyclopentyl)acetate were then added at 0° C. Stirring was continued for a further 2 h, and water and ethyl acetate were then added to the reaction mixture. The organic phase was washed with saturated sodium chloride solution and dried over magnesium sulfate. The crude product was purified by chromatography on silica gel (mobile phase cyclohexane/ethyl acetate 6:1 to 5:1). This gave 394 mg (50.2% of theory) of the target compound. Stirring was continued for a further 2 h The organic phase was washed with saturated sodium chloride solution dried over magnesium sulfate The crude product was purified by chromatography on silica gel (mobile phase cyclohexane/ethyl acetate 6:1 to 5:1)

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

実験手順: At 0° C., 280 mg (1.85 mmol) of 4-fluoro-2,3-dihydro-1H-isoindol-1-one were added to a suspension of 96.3 mg (2.41 mmol, 60% pure) of sodium hydride in 1 ml of DMF. The mixture was stirred for 30 min, and 654.5 mg (1.85 mmol) of tert-butyl(+/−)-[4-(bromomethyl)phenyl](cyclopentyl)acetate were then added at 0° C. Stirring was continued for a further 2 h, and water and ethyl acetate were then added to the reaction mixture. The organic phase was washed with saturated sodium chloride solution and dried over magnesium sulfate. The crude product was purified by chromatography on silica gel (mobile phase cyclohexane/ethyl acetate 6:1 to 5:1). This gave 394 mg (50.2% of theory) of the target compound. Stirring was continued for a further 2 h The organic phase was washed with saturated sodium chloride solution dried over magnesium sulfate The crude product was purified by chromatography on silica gel (mobile phase cyclohexane/ethyl acetate 6:1 to 5:1)

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

実験手順: 4.05 g (about 24.2 mmol) of 4-fluoro-3-hydroxy-2,3-dihydro-1H-isoindol-1-one were initially charged in 10 ml of dichloromethane, 22.4 ml (290.8 mmol) of trifluoroacetic acid and 7.7 ml (48.5 mmol) of triethylsilane were added and the mixture was stirred at RT overnight. The reaction mixture was then concentrated and the residue was dissolved in dichloromethane and washed with sodium bicarbonate solution. The crude product was purified by chromatography on silica gel (mobile phase cyclohexane/ethyl acetate 3:1 to 1:1). This gave 890 mg (24.2% of theory) of the target compound. The reaction mixture was then concentrated the residue was dissolved in dichloromethane washed with sodium bicarbonate solution The crude product was purified by chromatography on silica gel (mobile phase cyclohexane/ethyl acetate 3:1 to 1:1)

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

実験手順: 4.05 g (about 24.2 mmol) of 4-fluoro-3-hydroxy-2,3-dihydro-1H-isoindol-1-one were initially charged in 10 ml of dichloromethane, 22.4 ml (290.8 mmol) of trifluoroacetic acid and 7.7 ml (48.5 mmol) of triethylsilane were added and the mixture was stirred at RT overnight. The reaction mixture was then concentrated and the residue was dissolved in dichloromethane and washed with sodium bicarbonate solution. The crude product was purified by chromatography on silica gel (mobile phase cyclohexane/ethyl acetate 3:1 to 1:1). This gave 890 mg (24.2% of theory) of the target compound. The reaction mixture was then concentrated the residue was dissolved in dichloromethane washed with sodium bicarbonate solution The crude product was purified by chromatography on silica gel (mobile phase cyclohexane/ethyl acetate 3:1 to 1:1)

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

実験手順: At 0° C., 645 mg (4.27 mmol) of 4-fluoro-2,3-dihydro-1H-isoindol-1-one were added to 170.7 mg (4.27 mmol, 60% pure) of sodium hydride in 4 ml of DMF. The mixture was stirred for 30 min, and 2.11 g (5.98 mmol) of ethyl 2-[4-(bromomethyl)phenyl]-4,4,4-trifluoro-3-methylbutanoate were then added at 0° C. The reaction mixture was stirred for a further 2 h, and water and ethyl acetate were then added. The organic phase was washed with saturated sodium chloride solution and dried over magnesium sulfate. The crude product was purified by chromatography on silica gel (mobile phase cyclohexane/ethyl acetate 40:1 to 3:1). This gave 856 mg (33.9% of theory) of the target compound. The reaction mixture was stirred for a further 2 h The organic phase was washed with saturated sodium chloride solution dried over magnesium sulfate The crude product was purified by chromatography on silica gel (mobile phase cyclohexane/ethyl acetate 40:1 to 3:1)

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

実験手順: At 0° C., 280 mg (1.85 mmol) of 4-fluoro-2,3-dihydro-1H-isoindol-1-one were added to a suspension of 96.3 mg (2.41 mmol, 60% pure) of sodium hydride in 1 ml of DMF. The mixture was stirred for 30 min, and 654.5 mg (1.85 mmol) of tert-butyl(+/−)-[4-(bromomethyl)phenyl](cyclopentyl)acetate were then added at 0° C. Stirring was continued for a further 2 h, and water and ethyl acetate were then added to the reaction mixture. The organic phase was washed with saturated sodium chloride solution and dried over magnesium sulfate. The crude product was purified by chromatography on silica gel (mobile phase cyclohexane/ethyl acetate 6:1 to 5:1). This gave 394 mg (50.2% of theory) of the target compound. Stirring was continued for a further 2 h The organic phase was washed with saturated sodium chloride solution dried over magnesium sulfate The crude product was purified by chromatography on silica gel (mobile phase cyclohexane/ethyl acetate 6:1 to 5:1)

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

実験手順: 4.05 g (about 24.2 mmol) of 4-fluoro-3-hydroxy-2,3-dihydro-1H-isoindol-1-one were initially charged in 10 ml of dichloromethane, 22.4 ml (290.8 mmol) of trifluoroacetic acid and 7.7 ml (48.5 mmol) of triethylsilane were added and the mixture was stirred at RT overnight. The reaction mixture was then concentrated and the residue was dissolved in dichloromethane and washed with sodium bicarbonate solution. The crude product was purified by chromatography on silica gel (mobile phase cyclohexane/ethyl acetate 3:1 to 1:1). This gave 890 mg (24.2% of theory) of the target compound. The reaction mixture was then concentrated the residue was dissolved in dichloromethane washed with sodium bicarbonate solution The crude product was purified by chromatography on silica gel (mobile phase cyclohexane/ethyl acetate 3:1 to 1:1)