反应详情

温度

100 °C

To a solution of isopropyl ((2S,4R)-1-acetyl-6-bromo-2-methyl-1,2,3,4-tetrahydroquinolin-4-yl)carbamate (5 g, 13.54 mmol) and methyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate (3.90 g, 14.89 mmol) in DME (50 mL) and water (10.0 mL) were successively added palladium tetrakis(triphenylphosphine) (1.565 g, 1.354 mmol) and potassium carbonate (5.61 g, 40.6 mmol). The resulting mixture was stirred at 100° C. for 1 h, whereupon it was allowed to cool down to room temperature and was filtered through Celite™. The filtrated was concentrated in vacuo and the residue was partitioned between EtOAc and water. The aqueous phase was extracted with EtOAc (×3) and the combined organic layers were washed with brine, dried over MgSO4, filtered and concentrated in vacuo. The crude compound was purified by flash chromatography on a silica gel cartridge (50 g) eluting with EtOAc in cyclohexane (5-60%). The appropriate fractions were combined and concentrated under reduced pressure to give methyl 4-((2S,4R)-1-acetyl-4-((isopropoxycarbonyl)amino)-2-methyl-1,2,3,4-tetrahydroquinolin-6-yl)benzoate (4.64 g, 81%) as a white gum. LCMS (Formate, 2 min), Rt=1.09 min, MH+=425.

1. temperatureto cool down to room temperature
2. filtrationwas filtered through Celite™
3. concentrationThe filtrated was concentrated in vacuo
4. customthe residue was partitioned between EtOAc and water
5. extractionThe aqueous phase was extracted with EtOAc (×3)
6. washthe combined organic layers were washed with brine
7. dry with materialdried over MgSO4
8. filtrationfiltered
9. concentrationconcentrated in vacuo
10. customThe crude compound was purified by flash chromatography on a silica gel cartridge (50 g)
11. washeluting with EtOAc in cyclohexane (5-60%)
12. concentrationconcentrated under reduced pressure