反应详情

100 mmol (3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-ol in ethyl acetate were added onto 120 mmol of disuccimidylcarbonate (95%) in acetonitrile. Following, a solution of 140 mmol triethylamine in ethylacetate was added and stirred. The mixture was cooled and treated with a suspension of 92 mmol of 4-Amino-N-((2R,3S)-3-amino-2-hydroxy-4-phenylbutyl)-N-(isobutyl)benzene sulfonamide in ethyl acetate. 20 mmol methylamine, 41% aqueous solution in ethanol were added and the mixture was warmed. The reaction was washed twice with 10% Na2CO3-solution and with water. Solvent was evaporated and ethanol was added. Another portion of solvent was distilled off. The temperature was kept around 40-45° C. and crystallization was initiated by seeding. After stirring the mixture was cooled, stirred for another 90 min stirred, cooled and again stirred for 60 min. The precipitate was filtered and washed with ethanol. The wet product was dried in vacuo at 40° C. 43.5 g of (3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-yl (1S,2R)-3-[[(4-aminophenyl)sulfonyl](isobutyl) amino]-1-benzyl-2-hydroxypropylcarbamate were suspended in ethanol abs. and dissolved. The clear solution was cooled and seeding was applied. Crystallization occurred while cooling the mixture. Stirring was continued for another 60 min, followed by cooling, stirring and filtering off the product, which was washed with cold ethanol abs. The wet product was dried in vacuo at 40° C. Yield: 42.1 g=71%.

1. temperatureThe mixture was cooled
2. temperaturethe mixture was warmed
3. washThe reaction was washed twice with 10% Na2CO3-solution and with water
4. customSolvent was evaporated
5. additionethanol was added
6. distillationAnother portion of solvent was distilled off
7. customwas kept around 40-45° C.
8. customcrystallization
9. stirringAfter stirring the mixture
10. temperaturewas cooled
11. stirringstirred for another 90 min
12. stirringstirred
13. temperaturecooled
14. stirringagain stirred for 60 min
15. filtrationThe precipitate was filtered
16. washwashed with ethanol
17. customThe wet product was dried in vacuo at 40° C
18. dissolutionand dissolved
19. temperatureThe clear solution was cooled
20. customCrystallization
21. temperaturewhile cooling the mixture
22. stirringStirring
23. temperatureby cooling
24. stirringstirring
25. filtrationfiltering off the product, which
26. washwas washed with cold ethanol abs
27. customThe wet product was dried in vacuo at 40° C