反应详情

温度

0 °C

In a 25 mL round-bottomed flask, 45% hydrogen bromide in acetic acid (10 mL, 794 μmol) was added. It was cooled down to 0° C., then 2-tert-butoxy-2-oxoethyl 4-((2R,3S,4R,5S)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-neopentylpyrrolidine-2-carboxamido)-3-methoxybenzoate (580 mg, 794 μmol) was added as solid. After 30 min, the reaction mixture was concentrated, and water (50 mL) was added to the residue. It was extracted with methylene chloride (2×300 mL). The methylene chloride layers were combined, dried over anhydrous sodium sulfate, filtered and concentrated to give a crude product, which was purified by filtering through a short plug of silica gel to give 4-{[(2R,3S,4R,5S)-4-(4-chloro-2-fluoro-phenyl)-3-(3-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carbonyl]-amino}-3-methoxy-benzoic acid carboxymethyl ester as an off white solid (530 mg, 99% yield). LCMS (ES+) m/z calcd. for C33H32Cl2F2N3O6 [(M+H)+]: 674. found: 674.

1. concentrationthe reaction mixture was concentrated
2. additionwater (50 mL) was added to the residue
3. extractionIt was extracted with methylene chloride (2×300 mL)
4. dry with materialdried over anhydrous sodium sulfate
5. filtrationfiltered
6. concentrationconcentrated
7. customto give a crude product, which
8. customwas purified
9. filtrationby filtering through a short plug of silica gel