反应详情

Z-Asp(OtBu)-Ala-OBzl (43.6 g, 90 mmol) was dissolved in 1 liter DMF and hydrogenated in the presence of Tos-OH.H2O (17.1 g, 90 mmol) and 10% Pd-C. After the hydrogenation was completed the catalyst was filtered off. The filtrate was cooled to 0°, neutralized with N-methylmorpholine (9.9 ml, 90 mmol) and added to Z-Ser(tBu)-OSu. Another portion of N-methylmorpholine (9.9 ml, 90 mmol) was added and the reaction mixture was stirred at 0° for 1 h and at 25° for 18 h. 2-Diethylamino-ethylamine (2.83 ml, 20 mmol) was added to the reaction mixture and stirring was continued for 4 h. The solution was evaporated in vacuo, the residue dissolved in 0.5N NaOH (0.5 l) and extracted with ether (3×0.2 l). To the alkaline phase 0.4 l ethyl acetate was added and acidified with 5% KHSO4 /10% K2SO4 -solution. The acidic layer was again extracted with ethyl acetate (2×0.3 l). The combined organic layers were washed with 5% KHSO4 /10% K2SO4 -sol. (1×0.3 l) and saturated NaCl-sol., dried over Na2SO4, filtered and evaporated in vacuo.

1. filtrationwas filtered off
2. temperatureThe filtrate was cooled to 0°
3. stirringstirring
4. waitwas continued for 4 h
5. customThe solution was evaporated in vacuo
6. dissolutionthe residue dissolved in 0.5N NaOH (0.5 l)
7. extractionextracted with ether (3×0.2 l)
8. additionTo the alkaline phase 0.4 l ethyl acetate was added
9. extractionThe acidic layer was again extracted with ethyl acetate (2×0.3 l)
10. washThe combined organic layers were washed with 5% KHSO4 /10% K2SO4 -sol
11. dry with material, dried over Na2SO4
12. filtrationfiltered
13. customevaporated in vacuo