1-trimethylsilylpyrrolidin-2-one

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

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: Under a nitrogen atmosphere at a temperature of from -78° C. to -60° C., 180 ml of a 1.5 molar solution of lithium diisopropylamide (LDA) in cyclohexane are added dropwise to 31.4 g of N-trimethylsilylpyrrolid-2-one in 150 ml of tetrahydrofuran (THF) and the reaction mixture is stirred at the same temperature for a further one hour. Then, at from -78° C. to -60° C., 25.5 g of 2-chloro-5-chloromethylpyridine in 40 ml of THF are added, and the mixture is stirred for a further 16 hours at that temperature and then for a further three hours at room temperature. The reaction mixture is poured onto a mixture of ice/water and extracted with ethyl acetate, and the organic phase is separated off. The ethyl acetate phase is dried over sodium sulfate and concentrated to dryness by evaporation in vacuo. The residue is purified on silica gel using ethyl acetate/hexane (7:1) as eluant. The title compound having a melting point of 117-118° C. (compound 1.3) is obtained. the mixture is stirred for a further 16 hours at that temperature for a further three hours at room temperature extracted with ethyl acetate the organic phase is separated off The ethyl acetate phase is dried over sodium sulfate concentrated to dryness by evaporation in vacuo The residue is purified on silica gel is obtained

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

実験手順: Under a nitrogen atmosphere at a temperature of from -78° C. to -60° C., 180 ml of a 1.5 molar solution of lithium diisopropylamide (LDA) in cyclohexane are added dropwise to 31.4 g of N-trimethylsilylpyrrolid-2-one in 150 ml of tetrahydrofuran (THF) and the reaction mixture is stirred at the same temperature for a further one hour. Then, at from -78° C. to -60° C., 25.5 g of 2-chloro-5-chloromethylpyridine in 40 ml of THF are added, and the mixture is stirred for a further 16 hours at that temperature and then for a further three hours at room temperature. The reaction mixture is poured onto a mixture of ice/water and extracted with ethyl acetate, and the organic phase is separated off. The ethyl acetate phase is dried over sodium sulfate and concentrated to dryness by evaporation in vacuo. The residue is purified on silica gel using ethyl acetate/hexane (7:1) as eluant. The title compound having a melting point of 117-118° C. (compound 1.3) is obtained. the mixture is stirred for a further 16 hours at that temperature for a further three hours at room temperature extracted with ethyl acetate the organic phase is separated off The ethyl acetate phase is dried over sodium sulfate concentrated to dryness by evaporation in vacuo The residue is purified on silica gel is obtained

反応条件: temp:-76.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: In a flask was added diisopropylamine (3.22 g, 31.8 mmole) and dry THF (60 ml). The content of the flask was kept under nitrogen, and was then cooled to −76° C. To the cool solution was dropwise added n-butyllithium (n-BuLi, 32 mmole, 20 ml, 1.6 M in hexane). After completed addition, the solution was stirred for 10 minutes, and a solution of 1-Trimethylsilanyl-pyrrolidin-2-one (5.00 g, 31.8 mmole, prepared according to literature methods) in dry THF (5 ml) was added dropwise. The solution was then stirred for an additional 20 minutes and a solution of 4-Chlorobenzyl chloride (5.13 g, 32 mmole) in THF (5 ml) was added via a syringe during 5 minutes. The resulting mixture was stirred at −76° C. for 1 hour, and was then allowed to reach the ambient temperature and was stirred over night. Water (40 ml) was added and the mixture was stirred vigorously for 60 minutes. The phases were separated and the organic phase was washed with brine, and was finally evaporated, giving an oil which crystallized on standing. The solid was triturated with heptane:EtOAc 2:1 and was filtered, giving a partly purified solid. The solid was purified on silica (DCM to DCM:MeOH 99:1 to 98:2 to 97:3 gradient) giving 1.3 g (20%) of the sub-title compound. addition The solution was then stirred for an additional 20 minutes The resulting mixture was stirred at −76° C. for 1 hour the ambient temperature was stirred over night the mixture was stirred vigorously for 60 minutes The phases were separated the organic phase was washed with brine was finally evaporated giving an oil which crystallized The solid was triturated with heptane:EtOAc 2:1 was filtered giving a partly purified solid The solid was purified on silica (DCM to DCM:MeOH 99:1 to 98:2 to 97:3 gradient)

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

実験手順: To a solution of phosgen (6.12 g, 61.8 mmol) in anhydrous benzene (30 ml) was dropwise added under ice-cooling a solution of 2-nitrophenol (8.60 g, 61.8 mmol) and purified pyridine (4.88 g, 61.8 mmol) in anhydrous benzene (20 ml). The mixture was stirred for 30 min. at room temperature. From the reaction solution were separated precipitates by filtration, and a filtrate was evaporated under reduced pressure to give a colorless oily material. The oily material was dissolved in anhydrous benzene (20 ml), to which was added a solution of 1-trimethylsilyl-2-pyrrolidinone (4.00 g, 25.4 mmol) in anhydrous benzene (10 ml). The mixture was stirred at room temperature for 30 min. The reaction mixture was evaporated under reduced pressure to dryness to give a solid material. The desired product was separated using column chromatography on silica gel (eluted with chloroform-acetone 30:1→3:1). Recrystallization from ethanol afforded 1.98 g of colorless prisms. Yield 31.1% From the reaction solution were separated precipitates by filtration a filtrate was evaporated under reduced pressure to give a colorless oily material The mixture was stirred at room temperature for 30 min The reaction mixture was evaporated under reduced pressure to dryness to give a solid material The desired product was separated Recrystallization 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 of 4-bromophenyl chloroformate (4.19 g, 20.0 mmol) in anhydrous benzene (20 ml) was added a solution of 1-trimethylsilyl-2-pyrrolidinone (3.46 g, 22.0 mmol) in anhydrous benzene (10 ml). The mixture was stirred at room temperature for 30 min. The reaction mixture was evaporated under reduced pressure to dryness to give a solid material. Recrystallization from 2-propanol afforded 3.00 g of colorless prisms. Yield 53% The reaction mixture was evaporated under reduced pressure to dryness to give a solid material Recrystallization from 2-propanol