反应详情

H-Asp(OBzl)-OH (33.48 g, 150 mM) was suspended in DMF (400 ml). HOBT (2.03 g, 15 mM), BOC-Gln-ONP (55.10 g, 150 mM) and DMF (100 ml) were added thereto. The reaction mixture was adjusted to pH 7 by adding NMM (2 ml) at -10° C. and the mixture was stirred at room temperature overnight. The pH of the mixture was adjusted three times to pH 7 by adding NMM (16 ml). After the reaction (pH 6), the DMF was removed in vacuo. A citric acid solution (300 ml) and chloroform (300 ml) were added thereto and the mixture was shaken. The aqueous layer was extracted with chloroform (300 ml and 100 ml). The chloroform layers were combined and washed four times with saturated sodium chloride, acidic water (pH 3) and acidic water (pH 4), in that order. The aqueous layer was dried with anhydrous sodium sulfate and concentrated in vacuo. Ether was added to the residue and the precipitate formed was collected by filtration. Methanol was added to the collected precipitate and then the material was concentrated in vacuo, and then twice recrystallized from chloroform-ether to yield the substance [35] (32.31 g, yield: 47.7%). The mother liquor was concentrated in vacuo and recrystallized twice from chloroform-ether to obtain the substance [35] (6.3 g). Then the mother liquor was charged on a column of silica gel (100 g) and eluted with chloroform-ethanol-ethyl acetate (5:1:5). Corresponding fractions checked by TLC were dried in vacuo to obtain substance [35] (2.98 g). Total yield: 44.12 g (65.1%).

1. customAfter the reaction (pH 6)
2. customthe DMF was removed in vacuo
3. additionA citric acid solution (300 ml) and chloroform (300 ml) were added
4. stirringthe mixture was shaken
5. extractionThe aqueous layer was extracted with chloroform (300 ml and 100 ml)
6. washwashed four times with saturated sodium chloride, acidic water (pH 3) and acidic water (pH 4)
7. dry with materialThe aqueous layer was dried with anhydrous sodium sulfate
8. concentrationconcentrated in vacuo
9. additionEther was added to the residue
10. customthe precipitate formed
11. filtrationwas collected by filtration
12. additionMethanol was added to the collected precipitate
13. concentrationthe material was concentrated in vacuo
14. customtwice recrystallized from chloroform-ether