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

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 4-chloro-1-fluoro-2-nitrobenzene (9.2 g, 52.4 mmol), 4-amino-1-(4-methoxybenzyl)pyrrolidin-2-one (11.5 g, 52.4 mmol) and K2CO3 (14.5 g, 105 mmol) in 300 mL of anhydrous CH3CN was heated with stirring at 50° C. for 16 hours. The reaction mixture was filtered and the filter cake was dissolved with H2O (400 mL), and extracted with EtOAc (200 mL×4). The organic layers and the filtrate was combined and concentrated in vacuo to 50 mL. The precipitate was collected by filtration and washed with 10 mL of PE to afford 4-[(4-chloro-2-nitrophenyl)amino]-1-(4-methoxybenzyl)pyrrolidin-2-one as an orange solid (15.8 g, yield: 80.2%). was heated The reaction mixture was filtered the filter cake was dissolved with H2O (400 mL) extracted with EtOAc (200 mL×4) concentrated in vacuo to 50 mL The precipitate was collected by filtration washed with 10 mL of PE

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

Procedure: To a solution of 1-(4-methoxy-benzyl)-5-oxo-pyrrolidine-3-carboxylic acid amide (50.0 g, 201 mmol) in 560 mL of CH3CN and 560 mL of H2O was added bis(acetyloxy)(phenyl)-λ3-iodane (84.0 g, 261 mmol). The color of the mixture turned to light red. After being stirred at room temperature overnight, the reaction mixture was diluted with 1000 mL of H2O and acidified to pH 2 with concentrated HCl, then extracted with DCM (300 mL×3). The aqueous layer was then basified to pH 10 with 1 N aqueous solution of KOH and then extracted with DCM (400 mL×3). The combined organic layers were dried over Na2SO4 and then concentrated in vacuo to afford 4-amino-1-(4-methoxybenzyl)pyrrolidin-2-one as light yellow oil (28.0 g, yield: 63.2%), which solidified after being cooled down to room temperature and was used without further purification. extracted with DCM (300 mL×3) extracted with DCM (400 mL×3) The combined organic layers were dried over Na2SO4 concentrated in vacuo