反应详情

A suspension of 3.54 g of Fmoc-Asn-OH (10 mmol) and 5.2 g of triphenylmethanol (20 mmol) in 30 ml of acetic acid and 1.9 ml of acetic anhydride (20 mmol) is stirred at 50° for 15 minutes and then a solution of 0.05 ml of conc. sulfuric acid in 5 ml of acetic acid is added. After about one hour at 50° C. a solution forms, and after 11/2 hours a precipitate starts to form. After 3 hours, 200 ml of ice-cold water are slowly added to the suspension, while cooling in ice, the mixture is briefly stirred, and the precipitate is filtered off and thoroughly washed with water. The moist material is dissolved in ethyl acetate, and the organic phase is washed with a saturated aqueous sodium chloride solution, dried over sodium sulfate and concentrated under reduced pressure. Before the product starts to crystallize out, the solution is diluted with 1,2-dichloroethane, concentrated again and filtered through 50 g of silica gel. The excess triphenylmethanol is eluted with 200 ml of 1,2-dichloroethane, and then Fmoc-Asn(Trt)-OH is eluted with 500 ml each of a 98:2 and of a 96:4 mixture, of 1,2-dichloroethane and methanol. The residue after evaporation to dryness is dissolved in 10 ml of tetrahydrofuran, 30 ml of ethyl acetate are added, the solution is concentrated to 20 g, and diisopropyl ether is added to crystallize; the Fmoc-Asn(Trt)-OH obtainable in this way melts at 210°-211° (with decomposition).

1. waitAfter about one hour at 50° C. a solution forms
2. custom2 hours
3. customto form
4. waitAfter 3 hours
5. temperaturewhile cooling in ice
6. stirringthe mixture is briefly stirred
7. filtrationthe precipitate is filtered off
8. washthoroughly washed with water
9. dissolutionThe moist material is dissolved in ethyl acetate
10. washthe organic phase is washed with a saturated aqueous sodium chloride solution
11. dry with materialdried over sodium sulfate
12. concentrationconcentrated under reduced pressure
13. customto crystallize out
14. additionthe solution is diluted with 1,2-dichloroethane
15. concentrationconcentrated again
16. filtrationfiltered through 50 g of silica gel
17. washThe excess triphenylmethanol is eluted with 200 ml of 1,2-dichloroethane
18. washFmoc-Asn(Trt)-OH is eluted with 500 ml each of a 98:2 and of a 96:4 mixture, of 1,2-dichloroethane and methanol
19. customThe residue after evaporation to dryness
20. dissolutionis dissolved in 10 ml of tetrahydrofuran
21. addition30 ml of ethyl acetate are added
22. concentrationthe solution is concentrated to 20 g, and diisopropyl ether
23. additionis added
24. customto crystallize