反应详情

温度

4 °C

In 200 ml of THF was dissolved 15.7 g of acetyl-proline. To this solution were added under cooling with edible salt and ice 11.5 g of HOSu and 20.6 g of DCC, and the mixture was stirred for 21 hours at 4° C. The reaction liquid was filtered and the filtrate was evaporated whereby a semi-solid substance was obtained. This substance was recrystallized from isopropyl alcohol to obtain a white solid substance which was then dissolved in 400 ml of THF. To this solution was added 7.5 g of L-prolinol, and the mixture was stirred for 72 hours at room temperature. After removal of THF by distillation, the residue was dissolved in 300 ml of ethyl acetate and the solution was washed with 100 ml of 1-M Na2CO3, dehydrated with anhydrous Na2SO4 and evaporated until dryness. To the resultant oily substance were added 35.8 g of WBCD.HCl and 160 ml of redistilled DMSO, and the mixture was stirred for 10 minutes. Subsequently, 7.1 ml of a DMSO solution of 2-M anhydrous H3PO4 was added and the mixture was stirred for further 2 hours. The reaction was stopped with 300 ml of a buffer solution of 1-M potassium phosphate of pH 7.5. The reaction mixture was extracted with 350 ml of ethyl acetate, and the extract was dried over anhydrous Na2SO4. The ethyl acetate was distilled off and the residue was dissolved in 300 ml of ethanol. To this solution was added 200 g of NaHSO3 in 350 ml of water, and the mixture was stirred vigorously for 10 minutes. After concentration of the ethanol up to about 300 ml, unreacted materials were eliminated twice with 100 ml of ether, and solid Na2CO3 was added until the pH value of the liquid became 9. After 5 minutes, the reaction liquid was extracted twice with 100 ml of ether, and the ether was then distilled off to leave an oily substance. Yield 5.5 g (23.5%).

1. additionTo this solution were added
2. customThe reaction liquid
3. filtrationwas filtered
4. customthe filtrate was evaporated whereby a semi-solid substance
5. customwas obtained
6. customThis substance was recrystallized from isopropyl alcohol
7. customto obtain a white solid substance which
8. stirringthe mixture was stirred for 72 hours at room temperature
9. customAfter removal of THF
10. distillationby distillation
11. dissolutionthe residue was dissolved in 300 ml of ethyl acetate
12. washthe solution was washed with 100 ml of 1-M Na2CO3
13. customevaporated until dryness
14. additionTo the resultant oily substance were added 35.8 g of WBCD
15. stirringHCl and 160 ml of redistilled DMSO, and the mixture was stirred for 10 minutes
16. additionSubsequently, 7.1 ml of a DMSO solution of 2-M anhydrous H3PO4 was added
17. stirringthe mixture was stirred for further 2 hours
18. extractionThe reaction mixture was extracted with 350 ml of ethyl acetate
19. dry with materialthe extract was dried over anhydrous Na2SO4
20. distillationThe ethyl acetate was distilled off
21. dissolutionthe residue was dissolved in 300 ml of ethanol
22. additionTo this solution was added 200 g of NaHSO3 in 350 ml of water
23. stirringthe mixture was stirred vigorously for 10 minutes
24. additionwas added until the pH value of the liquid
25. waitAfter 5 minutes
26. customthe reaction liquid
27. extractionwas extracted twice with 100 ml of ether
28. distillationthe ether was then distilled off
29. customto leave an oily substance