反应详情

In a 250 ml round-bottomed flask (3S)-4-hydroxy-3-({[(phenylmethyl)oxy]carbonyl}amino)butanoic acid D1 (3.75 g), was dissolved in DMF (30 ml). To the resulting solution imidazole (3.02 g, 44.4 mmol), and TBDPSCl (7.61 ml, 29.6 mmol) were added and the resulting solution left under stirring at room temperature for 15 hours. The reaction mixture was transferred into separatory funnel containing water (300 ml). The pH of the medium was lowered to pH=2 by the addition of a 2 M HCl aqueous solution, then extracted with EtOAc (5×50 mls). The collected organic phase was dried (Na2SO4) and volatiles removed under reduced pressure to give a slightly yellow oil. This crude oil was transferred into a 250 ml round bottom flask with THF (50 ml) and MeOH (10 ml) was added. To the resulting mixture a K2CO3 aqueous solution (9 g of K2CO3 dissolved in 10 ml of water) was added and the reaction left under stirring at room temperature for 3 hours. Volatiles were removed under vacuum and the thick oil obtained was diluted in water (200 ml) and EtOAc (200 ml) and charged into a separatory funnel. The phases were separated and to the organic one water (200 ml) was added and the pH of the medium adjusted to pH=2 by the addition of a 2 M HCl aqueous solution. The phases were separated and the aqueous one back extracted with EtOAc (5×50 mls). The collected organic phases were dried (Na2SO4) and solvent removed under reduced pressure to give an oil that was purified by flash chromatography on silica gel (DCM/MeOH from 100/0 to 90/10). Collected fractions gave the title compound D2 (5.2 g) as a colorless oil. MS: (ES/+) m/z: 492 (M+1). C28H33NO5Si requires 491. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.05-8.28 (m, 4 H), 7.72-8.00 (m, 11 H), 5.47-5.59 (m, 2 H), 4.64-4.80 (m, 1 H), 4.17-4.34 (m, 2 H), 3.20-3.31 (m, 1 H), 3.06-3.20 (m, 1 H), 1.41-1.58 (m, 9 H).

1. waitthe resulting solution left
2. customThe reaction mixture was transferred into separatory funnel
3. extractionextracted with EtOAc (5×50 mls)
4. dry with materialThe collected organic phase was dried (Na2SO4)
5. customvolatiles removed under reduced pressure
6. customto give a slightly yellow oil
7. additionwas added
8. waitthe reaction left
9. stirringunder stirring at room temperature for 3 hours
10. customVolatiles were removed under vacuum
11. customthe thick oil obtained
12. customThe phases were separated and to the organic one water (200 ml)
13. additionwas added
14. additionthe pH of the medium adjusted to pH=2 by the addition of a 2 M HCl aqueous solution
15. customThe phases were separated
16. extractionthe aqueous one back extracted with EtOAc (5×50 mls)
17. dry with materialThe collected organic phases were dried (Na2SO4) and solvent
18. customremoved under reduced pressure
19. customto give an oil that
20. customwas purified by flash chromatography on silica gel (DCM/MeOH from 100/0 to 90/10)