1,1'-Carbonyldiimidazole → HCID 68799027, compound

Participants

Reaction Steps

1-{[1-(2-Cyclopentyloxycarbonylamino-3,3-dimethyl-butyryl)-4-hydroxy-pyrrolidine-2-carbonyl]-amino}-2-vinyl-cyclopropanecarboxylic acid methyl ester (530 mg, 1.11 mmol) was dissolved in CH2Cl2 (11 mL) and treated with CDI (234 mg, 1.44 mmol). After stirring overnight at room temperature, 4-fluoro-2,3-dihydro-1H-isoindole (762 mg, 5.56 mmol) was added and the reaction mixture was stirred overnight. The reaction was then diluted with CH2Cl2 and sequentially washed with 1N HCl, saturated aqueous NaHCO3, H2O and saturated aqueous NaCl. The organic phase was then dried over sodium sulfate. After removal of solvent, the crude product was purified by column chromatography on silica (40→60% EtOAc/Hexanes) to provide 4-fluoro-1,3-dihydro-isoindole-2-carboxylic acid 1-(2-cyclopentyloxycarbonylamino-3,3-dimethyl-butyryl)-5-(1-methoxycarbonyl-2-vinyl-cyclopropylcarbamoyl)-pyrrolidin-3-yl ester (563 mg, 79% yield). 1H NMR (CDCl3, 300 MHz) δ 7.77 (bd, 1H), 6.92-7.27 (m, 3H), 5.75 (m, 1H), 5.29 (m, 2H), 5.15 (m, 2H), 4.55-4.85 (m, 5H), 4.26 (m, 2H), 3.70 (m, 1H), 3.67 (s, 3H), 2.82 (m, 1H), 2.56 (m, 1H), 2.10 (m, 1H), 1.87 (m, 1H), 1.40-1.65 (m, 5H), 1.02 (s, 9H). LCMS found 643.3 [M+H]+.

Provenance & Evidence