反应详情

温度

-78 °C

SEM Fmoc amine 18c (0.212 g, 0.162 mmol, 1.0 eq.) was solubilised in THF (9.2 mL) and cooled to −78° C. under a nitrogen atmosphere. Super hydride solution (0.330 mL, 0.330 mmol, 2.04 eq.) was added drop wise over 4 minutes. After 45 minutes an aliquot was diluted with water and MeOH for LCMS After stirring for a further 10 mins, the reaction mixture was diluted with water (27 mL) and the cold bath removed. The organic layer was extracted with EtOAc (2×27 mL) and the combined organic extracts washed with brine (27 mL), dried over MgSO4, filtered and concentrated under reduced pressure. The crude product was dissolved in MeOH (11.05 mL), DCM (5.53 mL) and water (1.85 mL) and enough silica gel was added to form a thick suspension which was left stirring for 5 days. The suspension was filtered and washed with DCM/MeOH 9:1 (−200 mL) until complete elution of product. The organic layer was washed with brine (2×70 mL), dried over MgSO4, filtered and concentrated under reduced pressure. The resulting residue was purified by flash chromatography (silica gel; 40:1 v/v DCM/MeOH to 20:1 v/v DCM/MeOH) to afford the product as a yellow solid (0.060 g, 36%). LC/MS (2.802 min (ES+)), m/z: 1016.15 [M+H]+.

1. customthe cold bath removed
2. extractionThe organic layer was extracted with EtOAc (2×27 mL)
3. washthe combined organic extracts washed with brine (27 mL)
4. dry with materialdried over MgSO4
5. filtrationfiltered
6. concentrationconcentrated under reduced pressure
7. dissolutionThe crude product was dissolved in MeOH (11.05 mL)
8. additionDCM (5.53 mL) and water (1.85 mL) and enough silica gel was added
9. customto form a thick suspension which
10. waitwas left
11. stirringstirring for 5 days
12. filtrationThe suspension was filtered
13. washwashed with DCM/MeOH 9:1 (−200 mL) until complete elution of product
14. washThe organic layer was washed with brine (2×70 mL)
15. dry with materialdried over MgSO4
16. filtrationfiltered
17. concentrationconcentrated under reduced pressure
18. customThe resulting residue was purified by flash chromatography (silica gel; 40:1 v/v DCM/MeOH to 20:1 v/v DCM/MeOH)