反应详情

温度

0 °C

A portion of the crude (4S)-4-[(1R)-1-carboxy-but-3-enyl]-2,2-dimethyl-1,3-dioxolan-5-one from b) above (calculated from the NMR to contain 1.54 g, 7.19 mmol) and 1-hydroxy-7-aza-1H-1,2,3-benzotriazole (1.09 g, 7.55 mmol) in anhydrous dichloromethane (30 mL) were mixed and cooled to 0° C. under nitrogen. N-(Dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (1.60 g, 8.27 mmol) was added, and the mixture was stirred for 1.5 h at 0° C. (2S)-Amino-3,3-dimethyl-N-[(1R)-1-phenylethyl]butanamide hydrochloride (Preparation 1)(2.15 g, 7.55 mmol) was added, followed by diisopropylethylamine (1.37 mL, 7.55 mmol). After another 45 min, the mixture was allowed to warm to room temperature. After 3 h at room temperature, the mixture was partitioned between ethyl acetate (200 mL) and pH 7 aqueous phosphate buffer (100 mL). The organic layer was washed with sodium bicarbonate, brine, dried (Na2SO4), and concentrated under reduced pressure. The resulting foam crystallised upon addition of ether, and the white solid (1.89 g) was filtered off. Recystallisation from ethyl acetate/hexane gave (2R)-2-[(4S)-2,2-dimethyl-5-oxo-1,3-dioxolan-4-yl]-N-[(1S)-2,2-dimethyl-1-({[(1R)-1-phenylethyl]amino}carbonyl)propyl]pent-4-enamide as a white solid (1.30 g, 42%, as a single diastereomer).

1. additionwere mixed
2. additionwas added
3. temperatureto warm to room temperature
4. waitAfter 3 h at room temperature
5. customthe mixture was partitioned between ethyl acetate (200 mL) and pH 7 aqueous phosphate buffer (100 mL)
6. washThe organic layer was washed with sodium bicarbonate, brine
7. dry with materialdried (Na2SO4)
8. concentrationconcentrated under reduced pressure
9. customThe resulting foam crystallised upon addition of ether
10. filtrationthe white solid (1.89 g) was filtered off