[4-(chloromethyl)phenyl]-pyrrolidin-1-ylmethanone

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A suspension of potassium tert-butoxide (1.4 g) in anhydrous tetrahydrofuran (40 mL) at 0° C. was treated with a mixture of tert-butanol (1.0 mL) and 3-oxopentanoic acid methyl ester (1.3 mL). The mixture was stirred at 0° C. for 45 minutes and then a solution of (4-chloromethylphenyl)pyrrolidin-1-ylmethanone (2.0 g) in tetrahydrofuran (10 mL) was added and the resulting mixture heated at 70° C. for 24 hours. The mixture was cooled to room temperature, diluted with water and the tetrahydrofuran removed under reduced pressure. The residue was extracted with ethyl acetate and the combined extracts washed with saturated aqueous sodium chloride solution and dried over magnesium sulfate. The solvent was removed under reduced pressure and the residue purified by column chromatography on silica gel, eluting with a mixture of ethyl acetate and cyclohexane (3:7 by volume) to afford title compound, 1.1 g. the resulting mixture heated at 70° C. for 24 hours The mixture was cooled to room temperature the tetrahydrofuran removed under reduced pressure The residue was extracted with ethyl acetate the combined extracts washed with saturated aqueous sodium chloride solution dried over magnesium sulfate The solvent was removed under reduced pressure the residue purified by column chromatography on silica gel eluting with a mixture of ethyl acetate and cyclohexane (3:7 by volume)

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A suspension of potassium tert-butoxide (1.4 g) in anhydrous tetrahydrofuran (40 mL) at 0° C. was treated with a mixture of tert-butanol (1.0 mL) and 3-oxopentanoic acid methyl ester (1.3 mL). The mixture was stirred at 0° C. for 45 minutes and then a solution of (4-chloromethylphenyl)pyrrolidin-1-ylmethanone (2.0 g) in tetrahydrofuran (10 mL) was added and the resulting mixture heated at 70° C. for 24 hours. The mixture was cooled to room temperature, diluted with water and the tetrahydrofuran removed under reduced pressure. The residue was extracted with ethyl acetate and the combined extracts washed with saturated aqueous sodium chloride solution and dried over magnesium sulfate. The solvent was removed under reduced pressure and the residue purified by column chromatography on silica gel, eluting with a mixture of ethyl acetate and cyclohexane (3:7 by volume) to afford title compound, 1.1 g. the resulting mixture heated at 70° C. for 24 hours The mixture was cooled to room temperature the tetrahydrofuran removed under reduced pressure The residue was extracted with ethyl acetate the combined extracts washed with saturated aqueous sodium chloride solution dried over magnesium sulfate The solvent was removed under reduced pressure the residue purified by column chromatography on silica gel eluting with a mixture of ethyl acetate and cyclohexane (3:7 by volume)

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A suspension of potassium tert-butoxide (1.4 g) in anhydrous tetrahydrofuran (40 mL) at 0° C. was treated with a mixture of tert-butanol (1.0 mL) and 3-oxopentanoic acid methyl ester (1.3 mL). The mixture was stirred at 0° C. for 45 minutes and then a solution of (4-chloromethylphenyl)pyrrolidin-1-ylmethanone (2.0 g) in tetrahydrofuran (10 mL) was added and the resulting mixture heated at 70° C. for 24 hours. The mixture was cooled to room temperature, diluted with water and the tetrahydrofuran removed under reduced pressure. The residue was extracted with ethyl acetate and the combined extracts washed with saturated aqueous sodium chloride solution and dried over magnesium sulfate. The solvent was removed under reduced pressure and the residue purified by column chromatography on silica gel, eluting with a mixture of ethyl acetate and cyclohexane (3:7 by volume) to afford title compound, 1.1 g. the resulting mixture heated at 70° C. for 24 hours The mixture was cooled to room temperature the tetrahydrofuran removed under reduced pressure The residue was extracted with ethyl acetate the combined extracts washed with saturated aqueous sodium chloride solution dried over magnesium sulfate The solvent was removed under reduced pressure the residue purified by column chromatography on silica gel eluting with a mixture of ethyl acetate and cyclohexane (3:7 by volume)

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

実験手順: A solution of 4-chloromethylbenzoyl chloride (5.0 g) and pyrrolidine (2.2 mL) in dichloromethane (30 mL) at 0° C. was treated with ethyldiisopropylamine (5.2 mL). The resulting mixture was warmed to room temperature over 1 hour and then stirred at this temperature for 2 hours. The mixture was diluted with 1.0 M aqueous hydrochloric acid, extracted with dichloromethane and the combined extracts washed with saturated aqueous sodium chloride solution and then dried over magnesium sulfate. The solvent was removed under reduced pressure to afford title compound, 6.0 g. extracted with dichloromethane the combined extracts washed with saturated aqueous sodium chloride solution dried over magnesium sulfate The solvent was removed under reduced pressure

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

実験手順: A solution of 4-chloromethylbenzoyl chloride (5.0 g) and pyrrolidine (2.2 mL) in dichloromethane (30 mL) at 0° C. was treated with ethyldiisopropylamine (5.2 mL). The resulting mixture was warmed to room temperature over 1 hour and then stirred at this temperature for 2 hours. The mixture was diluted with 1.0 M aqueous hydrochloric acid, extracted with dichloromethane and the combined extracts washed with saturated aqueous sodium chloride solution and then dried over magnesium sulfate. The solvent was removed under reduced pressure to afford title compound, 6.0 g. extracted with dichloromethane the combined extracts washed with saturated aqueous sodium chloride solution dried over magnesium sulfate The solvent was removed under reduced pressure