反应详情

To a stirred solution of (S)—N-Boc-4-fluorophenylalanine (5.08 g, 17.9 mmol) and (S)-3-hydroxypyrrolidine (1.05 mL, 19.7 mmol) in anhydrous DMF (200 mL), was added DIPEA (6.87 mL, 39.5 mmol) and HOBt.H2O (3.02 g, 19.7 mmol). The reaction mixture was stirred for 10 min at room temperature then EDCI (4.13 g, 21.5 mmol) was added and the resulting mixture stirred for 20 h at rt. The volatiles were removed in vacuo then the residue partitioned between water (200 mL) and ethyl acetate (200 mL). The layers were separated and the aqueous layer extracted with ethyl acetate (3×50 mL). The combined organics were washed with aqueous sodium hydroxide solution (2M, 3×50 mL), brine (100 mL), dried (MgSO4), filtered and concentrated in vacuo. The oily residue was purified via flash chromatography (SiO2, methanol/dichloromethane, 1:19, v/v) to give the title compound as a colourless oil which became a white solid on standing. m/z (ES+)=353 [M+H]+; RT=3.17 min.

1. stirringthe resulting mixture stirred for 20 h at rt
2. customThe volatiles were removed in vacuo
3. customthe residue partitioned between water (200 mL) and ethyl acetate (200 mL)
4. customThe layers were separated
5. extractionthe aqueous layer extracted with ethyl acetate (3×50 mL)
6. washThe combined organics were washed with aqueous sodium hydroxide solution (2M, 3×50 mL), brine (100 mL)
7. dry with materialdried (MgSO4)
8. filtrationfiltered
9. concentrationconcentrated in vacuo
10. customThe oily residue was purified via flash chromatography (SiO2, methanol/dichloromethane, 1:19, v/v)