反应详情

温度

25 °C

On one hand, H-Val-Leu-OH (1 eq.) was added to a solution of MSA (2.72 eq.) in AcOEt. The slurry was stirred at 25° C. until a solution was obtained. The solution was then cooled to −15° C. On the other hand, Boc-Gly-Gly-OH (1.05 eq., commercially available) was added together with NMM (1.0 eq.), AcOEt and DMF. The slurry was stirred until complete dissolution and then cooled to −25° C. IBCF (1.0 eq.) was added to the Boc-Gly-Gly-OH solution to activate the carboxylic function. The silylated Val-Leu was then added and left to stir at least 30 min. The reaction mixture was conditioned to 25° C. before being quenched by the addition of water. The mixture was then diluted with AcOEt and washed with a solution of KHSO4 under stirring. The aqueous phase was discarded and the organic layer was washed again with a solution of NaCl. The organic phase was finally concentrated and the tetrapeptide crystallized under gentle stirring for at least 8 h at 5° C. The solid was recovered by filtration, once washed with cold AcOEt at 5° C. After drying under vacuum, 85% of Boc-Gly-Gly-Val-Leu-OH (SEQ ID NO 19) was recovered.

1. customwas obtained
2. temperatureThe solution was then cooled to −15° C
3. stirringThe slurry was stirred until complete dissolution
4. temperaturecooled to −25° C
5. waitleft
6. stirringto stir at least 30 min
7. customwas conditioned to 25° C.
8. custombefore being quenched by the addition of water
9. additionThe mixture was then diluted with AcOEt
10. washwashed with a solution of KHSO4
11. stirringunder stirring
12. washthe organic layer was washed again with a solution of NaCl
13. concentrationThe organic phase was finally concentrated
14. customthe tetrapeptide crystallized
15. stirringunder gentle stirring for at least 8 h at 5° C
16. filtrationThe solid was recovered by filtration
17. washonce washed with cold AcOEt at 5° C
18. dry with materialAfter drying under vacuum, 85% of Boc-Gly-Gly-Val-Leu-OH (SEQ ID NO 19)
19. customwas recovered