反应详情

Sodium hydride (704 mg, 60% in mineral oil, 17.6 mmol) was added to an ice-cooled solution of tert-butyl (3R)-3-hydroxypyrrolidine-1-carboxylate (J. Med. Chem. 1998, 41(25), 4983) (5 g, 26.7 mmol) in tetrahydrofuran (100 ml), and the mixture was allowed to warm to room temperature and stirred for 20 minutes. tert-Butyl bromoacetate (5.2 g, 26.7 mmol) was added and the mixture was heated under reflux for 18 hours, then cooled and concentrated under reduced pressure. The residue was partitioned between ethyl acetate and water and the phases separated. The organic layer was dried (MgSO4) and evaporated under reduced pressure. The crude product was purified by column chromatography on silica gel using an elution gradient of ethyl acetate:pentane (0:100 to 20:80) to afford the title compound, 1.95 g. 1H-NMR (CDCl3, 400 MHz) δ: 1.42 (s, 9H), 1.44 (s, 9H), 1.85-2.05 (m, 2H), 3.40 (m, 4H), 3.94 (m, 2H), 4.10 (m, 1H). LRMS: m/z (ES+) 324 [MNa+]

1. temperaturethe mixture was heated
2. temperatureunder reflux for 18 hours
3. temperaturecooled
4. concentrationconcentrated under reduced pressure
5. customThe residue was partitioned between ethyl acetate and water
6. customthe phases separated
7. dry with materialThe organic layer was dried (MgSO4)
8. customevaporated under reduced pressure
9. customThe crude product was purified by column chromatography on silica gel using an elution gradient of ethyl acetate:pentane (0:100 to 20:80)