反应详情

温度

100 °C

A mixture of 1-methylethyl[(2S,4R)-1-acetyl-2-methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,4-tetrahydro-4-quinolinyl]carbamate (for a preparation see Intermediate 52) (125 mg, 0.300 mmol), 1,1-dimethylethyl[2-(4-bromophenyl)ethyl]carbamate (90 mg, 0.300 mmol), potassium carbonate (104 mg, 0.751 mmol) and tetrakis(triphenylphosphine)palladium(0) (17.35 mg, 0.015 mmol) was degassed under house vacuum for 15 min and quenched several times with nitrogen, then was then stirred at 100° C. under nitrogen for 50 min before being cooled to room temperature. Most of the solvent was removed in vacuo and the residue was partitioned between AcOEt (20 mL) and water (15 mL). The layers were separated and the aqueous phase was extracted with AcOEt (15 mL). The combined organic phases were washed with brine (15 mL), dried over MgSO4 and concentrated in vacuo. Purification of the residue by flash chromatography on silica gel (gradient: 50 to 75% AcOEt in Hexanes) gave 1-methylethyl((2S,4R)-1-acetyl-6-{4-[2-({[(1,1-dimethylethyl)oxy]carbonyl}amino)ethyl]phenyl}-2-methyl-1,2,3,4-tetrahydro-4-quinolinyl)carbamate (50 mg, 0.093 mmol, 31%) as a colourless oil.

1. customwas degassed under house vacuum for 15 min
2. customquenched several times with nitrogen
3. temperaturebefore being cooled to room temperature
4. customMost of the solvent was removed in vacuo
5. customthe residue was partitioned between AcOEt (20 mL) and water (15 mL)
6. customThe layers were separated
7. extractionthe aqueous phase was extracted with AcOEt (15 mL)
8. washThe combined organic phases were washed with brine (15 mL)
9. dry with materialdried over MgSO4
10. concentrationconcentrated in vacuo
11. customPurification of the residue by flash chromatography on silica gel (gradient: 50 to 75% AcOEt in Hexanes)