1,1'-Carbonyldiimidazole → (S)-1-[4-(3-fluoro-benzyloxy)-phenyl]-5-oxo-pyrrolidine-3-carboxylic acid amide

Participants

Reaction Conditions

Reaction Steps

1,1′-carbonyldiimidazole (8.27 g, 51.0 mmol) was suspended and partly dissolved in tetrahydrofuran (110 mL) at 18° C. (S)-1-[4-(3-fluoro-benzyloxy)-phenyl]-5-oxo-pyrrolidine-3-carboxylic acid (14.0 g, 42.5 mmol; enantiomeric purity (S):(R)=99.5:0.5) was added as a solid together with tetrahydrofuran (30 mL) used for rinsing. The turbid solution, which turned into a white suspension after 15 min, was stirred 1 h at 16-20° C. and then transferred into a stirred 25% aqueous ammonia solution (7.95 mL) in tetrahydrofuran (80 mL). The last part of the white suspension was transferred with the aid of tetrahydrofuran (10 mL) for rinsing. After stirring for 0.5 h the reaction mixture was concentrated in vacuo to a volume of ˜70 mL and diluted with water (300 mL). Some ice was added to keep the temperature at 20-25° C. The white precipitate was collected by filtration, washed with water/tetrahydrofuran 80:20 and with heptane. Drying in vacuo at 20-45° C. afforded (S)-1-[4-(3-fluoro-benzyloxy)-phenyl]-5-oxo-pyrrolidine-3-carboxylic acid amide (13.5 g, 96%) as a white solid. The purity of the material by HPLC was 96.9% (area) and the enantiomeric ratio (S):(R) was determined as 99.7:0.3.

Provenance & Evidence