1-phenylpyrrolidin-2-one

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: 1-Phenyl-2-pyrrolidinone (1 g, 6.2 mmol) in THF (60 mL, anhydrous) was cooled to −40° C. and LiHMDS (8 mL, 8 mmol, 1 M soln. in THF) was added. The resulting solution was stirred for 40 min. and tosyl chloride (1.78 g, 9.33 mmol) was then added. After warming the solution to RT over a 14 hour period, H2O added to quench reaction. The solution was then concentrated to provide an oil. Next, the oil was redissovled in EtOAc and washed with H2O and brine. The organic layer was dried over Na2SO4, filtered, and concentrated to an oil once again. Purified via flash column chromatography (4:1 hexane/EtOAc) provided 3-chloro-1-phenylpyrrolidin-2-one. added to quench reaction The solution was then concentrated to provide an oil washed with H2O and brine The organic layer was dried over Na2SO4 filtered concentrated to an oil once again Purified via flash column chromatography (4:1 hexane/EtOAc)

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

Procedure: 1-Phenyl-2-pyrrolidinone (1 g, 6.2 mmol) in THF (60 mL, anhydrous) was cooled to −40° C. and LiHMDS (8 mL, 8 mmol, 1 M soln. in THF) was added. The resulting solution was stirred for 40 min. and tosyl chloride (1.78 g, 9.33 mmol) was then added. After warming the solution to RT over a 14 hour period, H2O added to quench reaction. The solution was then concentrated to provide an oil. Next, the oil was redissovled in EtOAc and washed with H2O and brine. The organic layer was dried over Na2SO4, filtered, and concentrated to an oil once again. Purified via flash column chromatography (4:1 hexane/EtOAc) provided 3-chloro-1-phenylpyrrolidin-2-one. added to quench reaction The solution was then concentrated to provide an oil washed with H2O and brine The organic layer was dried over Na2SO4 filtered concentrated to an oil once again Purified via flash column chromatography (4:1 hexane/EtOAc)

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

Procedure: The general procedure under argon was followed using copper(I) iodide (10 mg, 0.05 mmol), K3PO4 (425 mg, 2.00 mmol), 2-pyrrolidinone (91 μL, 1.20 mmol), iodobenzene (112 μL, 1.00 mmol), ethylene glycol (111 μL, 2.00 mmol) and 2-propanol (1.0 mL) at 90° C. Column chromatography using a solvent mixture (hexane/ethyl acetate=1/1) afforded N-(phenyl)-2-pyrrolidinone (80 mg, 50% isolated yield) as white solid. The spectral data (1H NMR) matched with the literature references and GC analysis indicated >95% purity. See Yin, J.; Buchwald, S. L. Org. Lett. 2000, 2, 1101-1104; and Kang, S.-K.; Lee, S.-H.; Lee, D. Synlett 2000, 1022-1024. at 90° C

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

Procedure: 1-Phenyl-2-pyrrolidinone (1 g, 6.2 mmol) in THF (60 mL, anhydrous) was cooled to −40° C. and LiHMDS (8 mL, 8 mmol, 1 M soln. in THF) was added. The resulting solution was stirred for 40 min. and tosyl chloride (1.78 g, 9.33 mmol) was then added. After warming the solution to RT over a 14 hour period, H2O added to quench reaction. The solution was then concentrated to provide an oil. Next, the oil was redissovled in EtOAc and washed with H2O and brine. The organic layer was dried over Na2SO4, filtered, and concentrated to an oil once again. Purified via flash column chromatography (4:1 hexane/EtOAc) provided 3-chloro-1-phenylpyrrolidin-2-one. added to quench reaction The solution was then concentrated to provide an oil washed with H2O and brine The organic layer was dried over Na2SO4 filtered concentrated to an oil once again Purified via flash column chromatography (4:1 hexane/EtOAc)

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Into a 150 mL sealed tube purged and maintained with an atmosphere of nitrogen, was placed 1-bromobenzene (4 g, 25.48 mmol). To this was added pyrrolidin-2-one (2.18 g, 25.65 mmol). Addition of Pd(OAc)2 (57 mg, 0.25 mmol) was next. This was followed by the addition of BINAP (240 mg, 0.39 mmol). This was followed by the addition of Cs2CO3 (12.5 g, 38.34=mol). To the mixture was added toluene (50 mL). The resulting solution was allowed to react, with stirring, overnight while the temperature was maintained at 120° C. in a bath of oil. The mixture was concentrated by evaporation under vacuum using a rotary evaporator. The residue was purified by eluting through a column with a 1:10 ethyl acetate/petroleum ether solvent system. This resulted in 1 g (24%) of 1-phenylpyrrolidin-2-one as yellow oil. Into a 150 mL sealed tube purged maintained with an atmosphere of nitrogen to react The mixture was concentrated by evaporation under vacuum a rotary evaporator The residue was purified by eluting through a column with a 1:10 ethyl acetate/petroleum ether solvent system This resulted in 1 g (24%) of 1-phenylpyrrolidin-2-one as yellow oil

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

Procedure: 1-Phenyl-2-pyrrolidinone (1 g, 6.2 mmol) in THF (60 mL, anhydrous) was cooled to −40° C. and LiHMDS (8 mL, 8 mmol, 1 M soln. in THF) was added. The resulting solution was stirred for 40 min. and tosyl chloride (1.78 g, 9.33 mmol) was then added. After warming the solution to RT over a 14 hour period, H2O added to quench reaction. The solution was then concentrated to provide an oil. Next, the oil was redissovled in EtOAc and washed with H2O and brine. The organic layer was dried over Na2SO4, filtered, and concentrated to an oil once again. Purified via flash column chromatography (4:1 hexane/EtOAc) provided 3-chloro-1-phenylpyrrolidin-2-one. added to quench reaction The solution was then concentrated to provide an oil washed with H2O and brine The organic layer was dried over Na2SO4 filtered concentrated to an oil once again Purified via flash column chromatography (4:1 hexane/EtOAc)

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

Procedure: 8.06 g of N-phenylpyrrolidinone were dissolved in 33 ml glacial acetic acid; the mixture was cooled to 0°-5° C. and then a solution of 2.65 ml bromine in 12 ml of glacial acetic acid was added dropwise. Stirring was continued for 30 minutes at room temperature. Work-up was accomplished by pouring the mixture into 1 l of water and neutralizing the mixture with KOH. The solid was filtered and dissolved in ethylacetate and washed with a sodium thiosulphate solution until the brown colour disappeared; washing with brine and drying with MgSO4 provided 8.5 g of a white crystalline mass that could be recrystallized from ether; m.p. 102° C. the mixture was cooled to 0°-5° C. The solid was filtered dissolved in ethylacetate washed with a sodium thiosulphate solution until the brown colour washing with brine drying with MgSO4 provided 8.5 g of a white crystalline mass that could be recrystallized from ether

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

Procedure: 8.06 g of N-phenylpyrrolidinone were dissolved in 33 ml glacial acetic acid; the mixture was cooled to 0°-5° C. and then a solution of 2.65 ml bromine in 12 ml of glacial acetic acid was added dropwise. Stirring was continued for 30 minutes at room temperature. Work-up was accomplished by pouring the mixture into 1 l of water and neutralizing the mixture with KOH. The solid was filtered and dissolved in ethylacetate and washed with a sodium thiosulphate solution until the brown colour disappeared; washing with brine and drying with MgSO4 provided 8.5 g of a white crystalline mass that could be recrystallized from ether; m.p. 102° C. the mixture was cooled to 0°-5° C. The solid was filtered dissolved in ethylacetate washed with a sodium thiosulphate solution until the brown colour washing with brine drying with MgSO4 provided 8.5 g of a white crystalline mass that could be recrystallized from ether

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

Procedure: The general procedure under argon was followed using copper(I) iodide (10 mg, 0.05 mmol), K3PO4 (425 mg, 2.00 mmol), 2-pyrrolidinone (91 μL, 1.20 mmol), Iodobenzene (112 μL, 1.00 mmol), ethylene glycol (111 μL, 2.00 mmol) and 2-propanol (1.0 mL) at 90° C. Column chromatography using a solvent mixture (hexane/ethyl acetate=1/1) afforded N-(phenyl)-2-pyrrolidinone (80 mg, 50% isolated yield) as white solid. The spectral data (1H NMR) matched with the literature references and GC analysis indicated >95% purity. See Yin, J.; Buchwald, S. L. Org. Lett. 2000, 2, 1101-1104; and Kang, S.-K.; Lee, S.-H.; Lee, D. Synlett 2000, 1022-1024. at 90° C

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

Procedure: The general procedure under argon was followed using copper(I) iodide (10 mg, 0.05 mmol), K3PO4 (425 mg, 2.00 mmol), 2-pyrrolidinone (91 μL, 1.20 mmol), Iodobenzene (112 μL, 1.00 mmol), ethylene glycol (111 μL, 2.00 mmol) and 2-propanol (1.0 mL) at 90° C. Column chromatography using a solvent mixture (hexane/ethyl acetate=1/1) afforded N-(phenyl)-2-pyrrolidinone (80 mg, 50% isolated yield) as white solid. The spectral data (1H NMR) matched with the literature references and GC analysis indicated >95% purity. See Yin, J.; Buchwald, S. L. Org. Lett. 2000, 2, 1101-1104; and Kang, S. -K.; Lee, S. -H.; Lee, D. Synlett 2000, 1022-1024. at 90° C