1,1'-Carbonyldiimidazole → Imidazolin-2-one, 8

Participants

Reaction Steps

To a solution of (2R,3R)-3-(tert-Butyldimethylsilanyloxy)-2-[(3-chloro-4-cyano-2-methylphenylamino)methyl]pyrrolidine-1-carboxylic acid tert-butyl ester (51E) (22 mg, 0.06 mmol) dissolved in THF (1 mL) was added 1,1′-carbonyldiimidazole (9.40 mg, 0.06 mmol) and the mixture was stirred at rt for 3 days, and then brought to reflux for 1 h. An aliquot (˜half of the reaction mixture) was treated with DBU (10 μL, 0.07 mmol) and the reaction mixture was heated at reflux overnight. The reaction was then diluted with EtOAc and water, and the layers were separated. The organic layer was washed with brine, concentrated under reduced pressure, and purified via preparative HPLC (Luna C-18, 21.2×100 mm, eluting with 60-100% solvent B (A=90% H2O—10% MeOH—0.1% TFA and B=10% H2O—90% MeOH—0.1% TFA) over 12 min; Flow rate at 20 mL/min. UV detection at 220 nm). The major peak was collected, concentrated and treated with TFA (2 mL) overnight. The reaction was concentrated and purified via preparative HPLC (Luna C-18, 21.2×100 mm, eluting with 40-100% solvent B (A=90% H2O—10% MeOH—0.1% TFA and B=10% H2O—90% MeOH—0.1% TFA) over 10 min; Flow rate at 20 mL/min. UV detection at 220 nm) to provide the title compound (1 mg). LC/MS m/z 292 [M+H]+.

Provenance & Evidence