反应详情

温度

0 °C

Tert-butyl (S)-3-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-4-oxo-4-(piperidin-1-yl)butanoate (Compound SP403) (9.3 g, 19.4 mmol) was dissolved in toluene (300 mL), and the mixture was concentrated under reduced pressure. This operation was further repeated twice, and the residue was dried under reduced pressure overnight. Dehydrated dichloromethane (8.6 ml) was placed in the reaction vessel, and the mixture was stirred at 0° C. for 5 minutes under a nitrogen atmosphere, followed by dropwise addition of trifluoroacetic acid (8.6 ml, 116 mmol). After stirring at room temperature for 4 hours, triethylamine (16.2 ml, 116 mmol) was added dropwise at 0° C. The reaction mixture was diluted with dichloromethane (100 ml), and the organic layer was washed with a 5% aqueous sodium dihydrogenphosphate solution six times. The organic extract was dried over sodium sulfate and then concentrated under reduced pressure. The resulting residue was diluted again with dichloromethane (100 ml), and the organic layer was washed with a 5% aqueous sodium dihydrogenphosphate solution twice. The organic extract was dried over sodium sulfate and then concentrated under reduced pressure to afford (S)-3-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-4-oxo-4-(piperidin-1-yl)butanoic acid (Fmoc-Asp-pip, Compound SP401) (7.8 g, 96%). This compound was used in the next step without further purification.

1. concentrationthe mixture was concentrated under reduced pressure
2. customthe residue was dried under reduced pressure overnight
3. stirringAfter stirring at room temperature for 4 hours
4. washthe organic layer was washed with a 5% aqueous sodium dihydrogenphosphate solution six times
5. extractionThe organic extract
6. dry with materialwas dried over sodium sulfate
7. concentrationconcentrated under reduced pressure
8. additionThe resulting residue was diluted again with dichloromethane (100 ml)
9. washthe organic layer was washed with a 5% aqueous sodium dihydrogenphosphate solution twice
10. extractionThe organic extract
11. dry with materialwas dried over sodium sulfate
12. concentrationconcentrated under reduced pressure