反应详情

A mixture of palladium acetate (17 mg, 0.075 mmol) and tri-(2-methylphenyl)phosphine (46 mg, 0.15 mmol) in anhydrous acetonitrile (2 mL) was sonicated at room temperature for 1 min until a creamy-coloured suspension formed. This suspension was added via Pasteur pipette to a stirred solution of (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 (650 mg, 1.5 mmol), 1-bromo-3-fluoro-4-phenoxybenzene (Preparation 10)(587 mg, 2.26 mmol), and N-ethylmorpholine (348 μL, 3.0 mmol) in anhydrous acetonitrile (2.5 mL) under nitrogen. The mixture was purged with nitrogen, then heated at reflux for 16 h. After being cooled, the mixture was poured into ethyl acetate (100 mL) and washed with 5% aqueous citric acid (30 mL), saturated aqueous sodium chloride (50 mL), dried (NaSO4), and concentrated under reduced pressure. The residue was purified by flash chromatography (gradient elution with dichloromethane:ether) to give mainly (2R, 5E)-2-[(4S)-2,2-dimethyl-5-oxo-1,3-dioxolan-4-yl]-N-[(1S)-2,2-dimethyl-1-({[(1R)-1-phenylethyl]amino}carbonyl)propyl]-5-(3-fluoro-4-phenoxyphenyl)pent-4-enamide as a pale yellow foam (210 mg, 22%). 1H nmr suggested that alkene isomers were also present. The mixture of alkenes was taken onto the next step (see b, below).

1. customwas sonicated at room temperature for 1 min until a creamy-coloured suspension
2. customformed
3. customThe mixture was purged with nitrogen
4. temperatureheated
5. temperatureat reflux for 16 h
6. temperatureAfter being cooled
7. additionthe mixture was poured into ethyl acetate (100 mL)
8. washwashed with 5% aqueous citric acid (30 mL), saturated aqueous sodium chloride (50 mL)
9. dry with materialdried (NaSO4)
10. concentrationconcentrated under reduced pressure
11. customThe residue was purified by flash chromatography (gradient elution with dichloromethane:ether)