5-benzylpyrrolidin-2-one

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a 2 M lithium diisopropylamine solution in THF of −78° C. is added 5-benzylpyrrolidin-2-one and the mixture is stirred for 1.5 hours at −78° C. Then 1-propyl bromide is added and the reaction is stirred for another 1.5 hours at −78° C. The reaction mixture is allowed to warm up to 0° C. before ice-cold water with acetic acid is added and subsequently extracted 3 times with dichloromethane. The dichloromethane is concentrated in vacuo and the residue is dissolved in dichloromethane, washed with saturated NaHCO3 and brine. Crude 5-benzyl-3-propyldihydrofuran-2(3H)-one is obtained after removal of the solvents in vacuo. The product is purified by column chromatography. the reaction is stirred for another 1.5 hours at −78° C is added subsequently extracted 3 times with dichloromethane The dichloromethane is concentrated in vacuo the residue is dissolved in dichloromethane washed with saturated NaHCO3 and brine

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a 2 M lithium diisopropylamine solution in THF of −78° C. is added 5-benzylpyrrolidin-2-one and the mixture is stirred for 1.5 hours at −78° C. Then 1-propyl bromide is added and the reaction is stirred for another 1.5 hours at −78° C. The reaction mixture is allowed to warm up to 0° C. before ice-cold water with acetic acid is added and subsequently extracted 3 times with dichloromethane. The dichloromethane is concentrated in vacuo and the residue is dissolved in dichloromethane, washed with saturated NaHCO3 and brine. Crude 5-benzyl-3-propylpyrrolidin-2-one is obtained after removal of the solvents in vacuo. The product is purified by column chromatography. the reaction is stirred for another 1.5 hours at −78° C is added subsequently extracted 3 times with dichloromethane The dichloromethane is concentrated in vacuo the residue is dissolved in dichloromethane washed with saturated NaHCO3 and brine

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

Procedure: 5-Benzylpyrrolidin-2-one is synthesized from pyrrolidine-2,5-dione and benzyl bromide according to S. Lebrun et al. (Tetrahedron Asymmetry 2003, 14, 2625-2632).

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

Procedure: Methylate 5-benzylpyrrolidin-2-one with methyl iodide in the presence of potassium carbonate in ethyl methyl ketone; nitrate the thus-obtained 5-benzyl-1-methylpyrrolidin-2-one with nitric acid/sulfuric acid, pour the resulting reaction product onto ice water, extract it with methylene chloride, evaporate solvent from the extract and hydrogenate the thus-obtained 1-methyl-5-(4-nitrobenzyl)pyrrolidin-2-one with platinum/hydrogen without further purification to obtain 5-(4-aminobenzyl)-1-methylpyrrolidin-2-one. the resulting reaction product onto ice water extract it with methylene chloride evaporate solvent from the extract without further purification