反应详情

A solution of (2R,3S)-2-((tert-butoxycarbonyl)amino)-3-hydroxybutanoic acid (Frontier Scientific, Utah) (9.94 g, 45.3 mmol) in DCM (100 mL) was treated with 2,6-dimethylpyridine (Fluka) (15.79 mL, 136 mmol). A solution of tert-butyldimethylsilyl trifluoromethanesulfonate (Fluka) (22.9 mL, 100 mmol) in DCM (50 mL) was added dropwise over 1 h. The mixture was stirred for an additional 2 h, after which time the reaction was complete by LC-MS analysis. The mixture was diluted with saturated brine (100 mL) and acidified with a slight excess of 1.0 M aq. HCl. The mixture was stirred for 30 min, the layers were separated, and the aq. layer was extracted with DCM (100 mL). The combined organic extracts were dried (MgSO4) and concentrated to give crude product as a white semi-solid (26 g). The crude product was dissolved in MeOH (25 mL) and a solution of anhydrous Na2CO3 (4.80 g, 45.3 mmol) in water (25 mL) was added dropwise. The solution was stirred for 15 min and then concentrated to remove the MeOH. The resulting oily solution was diluted with water (175 mL) and hexane (200 mL) and stirred for 15 min. The aq. layer was separated and washed with a further 200 mL of hexane. The aq. layer was separated, diluted with DCM (200 mL), and 1.0 M aq. HCl was added dropwise to the stirred mixture. The mixture was separated and the aq. layer extracted with DCM (100 mL). The combined organic layers were dried (MgSO4) and concentrated to give (2R,3S)-2-((tert-butoxycarbonyl)amino)-3-((tert-butyldimethylsilyl)oxy)butanoic acid (615a) (14.52 g, 43.5 mmol, 96% yield) as a colorless viscous oil. LC-MS m/z 356.1 [M+Na]1.

1. stirringThe mixture was stirred for 30 min
2. customthe layers were separated
3. extractionthe aq. layer was extracted with DCM (100 mL)
4. dry with materialThe combined organic extracts were dried (MgSO4)
5. concentrationconcentrated
6. customto give crude product as a white semi-solid (26 g)
7. stirringThe solution was stirred for 15 min
8. concentrationconcentrated
9. customto remove the MeOH
10. additionThe resulting oily solution was diluted with water (175 mL) and hexane (200 mL)
11. stirringstirred for 15 min
12. customThe aq. layer was separated
13. washwashed with a further 200 mL of hexane
14. customThe aq. layer was separated
15. additiondiluted with DCM (200 mL), and 1.0 M aq. HCl
16. additionwas added dropwise to the stirred mixture
17. customThe mixture was separated
18. extractionthe aq. layer extracted with DCM (100 mL)
19. dry with materialThe combined organic layers were dried (MgSO4)
20. concentrationconcentrated