1-[(4-methoxyphenyl)methyl]pyrrolidin-2-one

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of diisopropylamine (4.1 mL) in tetrahydrofuran (25 mL) was added dropwise n-butyllithium (1.6 M hexane solution, 18 mL) at −78° C. under nitrogen atmosphere, and the mixture was warmed to 0° C., and stirred for 30 min. The reaction mixture was cooled to −78° C., a solution of 1-(4-methoxybenzyl)pyrrolidin-2-one (5.0 g) obtained in Step A in tetrahydrofuran (25 mL) was added thereto, and the mixture was stirred at the same temperature for 1 hr. Iodoethane (2.9 mL) was added thereto, and the mixture was stirred overnight while it was allowed to be warmed. To the reaction mixture was added saturated aqueous ammonium chloride solution, and the mixture was extracted with ethyl acetate. The obtained organic layer was washed with saturated brine, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate) to give the title compound (2.8 g). The reaction mixture was cooled to −78° C. the mixture was stirred at the same temperature for 1 hr the mixture was stirred overnight while it to be warmed the mixture was extracted with ethyl acetate The obtained organic layer was washed with saturated brine dried over anhydrous magnesium sulfate the solvent was evaporated under reduced pressure The residue was purified by silica gel column chromatography (hexane/ethyl acetate)

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

Procedure: To a solution of pyrrolidin-2-one (15 g) in a mixed solvent of tetrahydrofuran/N,N-dimethylformamide (1/1, 100 mL) was added sodium hydride (60% in mineral oil, 8.5 g) at 0° C. under nitrogen atmosphere, and the mixture was stirred for 30 min. p-Methoxybenzyl chloride (33 g) was added thereto at the same temperature, and the mixture was stirred at room temperature for 5 hr. To the reaction mixture was added water, and the mixture was extracted with ethyl acetate. The obtained organic layer was washed successively with water and saturated brine, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate) to give the title compound (28 g). was added the mixture was extracted with ethyl acetate The obtained organic layer was washed successively with water and saturated brine dried over anhydrous magnesium sulfate the solvent was evaporated under reduced pressure The residue was purified by silica gel column chromatography (hexane/ethyl acetate)

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

Procedure: To a solution of pyrrolidin-2-one (15 g) in a mixed solvent of tetrahydrofuran/N,N-dimethylformamide (1/1, 100 mL) was added sodium hydride (60% in mineral oil, 8.5 g) at 0° C. under nitrogen atmosphere, and the mixture was stirred for 30 min. p-Methoxybenzyl chloride (33 g) was added thereto at the same temperature, and the mixture was stirred at room temperature for 5 hr. To the reaction mixture was added water, and the mixture was extracted with ethyl acetate. The obtained organic layer was washed successively with water and saturated brine, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate) to give the title compound (28 g). was added the mixture was extracted with ethyl acetate The obtained organic layer was washed successively with water and saturated brine dried over anhydrous magnesium sulfate the solvent was evaporated under reduced pressure The residue was purified by silica gel column chromatography (hexane/ethyl acetate)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of diisopropylamine (4.1 mL) in tetrahydrofuran (25 mL) was added dropwise n-butyllithium (1.6 M hexane solution, 18 mL) at −78° C. under nitrogen atmosphere, and the mixture was warmed to 0° C., and stirred for 30 min. The reaction mixture was cooled to −78° C., a solution of 1-(4-methoxybenzyl)pyrrolidin-2-one (5.0 g) obtained in Step A in tetrahydrofuran (25 mL) was added thereto, and the mixture was stirred at the same temperature for 1 hr. Iodoethane (2.9 mL) was added thereto, and the mixture was stirred overnight while it was allowed to be warmed. To the reaction mixture was added saturated aqueous ammonium chloride solution, and the mixture was extracted with ethyl acetate. The obtained organic layer was washed with saturated brine, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate) to give the title compound (2.8 g). The reaction mixture was cooled to −78° C. the mixture was stirred at the same temperature for 1 hr the mixture was stirred overnight while it to be warmed the mixture was extracted with ethyl acetate The obtained organic layer was washed with saturated brine dried over anhydrous magnesium sulfate the solvent was evaporated under reduced pressure The residue was purified by silica gel column chromatography (hexane/ethyl acetate)

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

Procedure: To a solution of pyrrolidin-2-one (15 g) in a mixed solvent of tetrahydrofuran/N,N-dimethylformamide (1/1, 100 mL) was added sodium hydride (60% in mineral oil, 8.5 g) at 0° C. under nitrogen atmosphere, and the mixture was stirred for 30 min. p-Methoxybenzyl chloride (33 g) was added thereto at the same temperature, and the mixture was stirred at room temperature for 5 hr. To the reaction mixture was added water, and the mixture was extracted with ethyl acetate. The obtained organic layer was washed successively with water and saturated brine, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate) to give the title compound (28 g). was added the mixture was extracted with ethyl acetate The obtained organic layer was washed successively with water and saturated brine dried over anhydrous magnesium sulfate the solvent was evaporated under reduced pressure The residue was purified by silica gel column chromatography (hexane/ethyl acetate)