反应详情

To a solution of (S)-benzyl 4-(3-(1,3-dioxoisoindolin-2-yl)propyl)-5-oxooxazolidine-3-carboxylate (11.6 g, 28.40 mmol) in DCM (30.0 mL) was added Et3SiH (13.6 mL, 85.3 mmol). The reaction mixture was stirred overnight. The mixture was concentrated under reduced pressure and dissolved in THF (100 mL). To this THY solution was added tert-butyl chloroformate (4.4 mL, 34.08 mmol) at 0° C. followed by TEA (12.0 mL, 85.2 mmol) and stirred at RT for 30 min. The precipitate was filtered off and the filtrate was added into a NaBH4 suspension in water (1.0 mL) at 0° C., and the mixture was stirred at RT for 30 min. LC/MS indicated the completion of the reaction. The mixture was acidified to pH 3 using HCl (1 N). The aqueous layer was extracted with EtOAc (300 mL×2). The combined organic layer was washed with NaHCO3, brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude was purified on silica gel column using a mixture of EtOAc and hexanes to give (S)-benzyl 5-(1,3-dioxoisoindolin-2-yl)-1-hydroxypentan-2-yl(methyl)carbamate (5.01 g, 45%). LRMS (M+H+) m/z 397.3.

1. concentrationThe mixture was concentrated under reduced pressure
2. dissolutiondissolved in THF (100 mL)
3. stirringstirred at RT for 30 min
4. filtrationThe precipitate was filtered off
5. additionthe filtrate was added into a NaBH4 suspension in water (1.0 mL) at 0° C.
6. stirringthe mixture was stirred at RT for 30 min
7. customthe completion of the reaction
8. extractionThe aqueous layer was extracted with EtOAc (300 mL×2)
9. washThe combined organic layer was washed with NaHCO3, brine
10. dry with materialdried over Na2SO4
11. filtrationfiltered
12. concentrationconcentrated under reduced pressure
13. customThe crude was purified on silica gel column
14. additiona mixture of EtOAc and hexanes