反应详情

Crude (S)-methyl 2-((S)-2-amino-3-hydroxypropanamido)-3-(3-(benzyloxy)-4-methoxyphenyl)propanoate (TFA salt, 8.7 mmol) was dissolved in DMF (50 mL) followed by addition of 2-morpholinoacetic acid (1.3 g, 8.7 mmol), HATU (5.0 g, 13.1 mmol) and DIPEA (5.0 mL) at 0° C. with stirring. The reaction mixture was allowed to warm to ambient temperature and stirred for 3 h. EtOAc (200 mL) and water (200 mL) was added and two layers were separated. The aqueous phase was extracted with EtOAc (100 mL×3) and the combined organic phases were washed with brine (200 mL×3), dried over anhydrous sodium sulfate, and concentrated. The residue was purified by flash column chromatography on silica gel (CH2Cl2/EtOAc/MeOH=20:10:1) to afford (S)-methyl 3-(3-(benzyloxy)-4-methoxyphenyl)-2-((S)-3-hydroxy-2-(2-morpho linoacetamido)propanamido)propanoate (2.9 g, 62% yield).

1. stirringstirred for 3 h
2. customtwo layers were separated
3. extractionThe aqueous phase was extracted with EtOAc (100 mL×3)
4. washthe combined organic phases were washed with brine (200 mL×3)
5. dry with materialdried over anhydrous sodium sulfate
6. concentrationconcentrated
7. customThe residue was purified by flash column chromatography on silica gel (CH2Cl2/EtOAc/MeOH=20:10:1)