反应详情

A solution of Example 168B (0.2 g, 0.67 mmol), 1-but-3-ynyl-(2R)-2-methyl-pyrrolidine (7.4 mL as a 0.1 M solution in acetonitrile, 0.74 mmol), and triethylamine (10 mL, 72.0 mmol) was degassed with nitrogen for 10 minutes while stirring at r.t. Next, Pd(PPh3)2Cl2 (0.010 g, 0.013 mmol) and CuI (0.003 g, 0.013 mmol) were added and the resulting mixture was degassed for an additional 10 minutes, sealed, and stirred at r.t. for 18 hours. Contents were then concentrated under reduced pressure and the residue was dissolved in 100 mL dichloromethane, washed twice with each: 50 mL sat. NaHCO3, 50 mL water, and 50 mL brine, dried with Na2SO4, and concentrated under reduced pressure. The crude material was purified by column chromatography (100% dichloromethane to 95:5 dichloromethane/methanol) to afford the product in 30% yield as a light yellow oil. 1H NMR (CD3OD, 300 MHz) δ 7.03 (d, J=9 Hz, 1H), 6.88 (d, J=3 Hz, 1H), 6.68 (dd, J=3, 9 Hz, 1H), 3.41-3.20 (m, 2H), 2.79-2.52 (m, 5H), 2.12-2.04 (m, 1H), 1.92-1.82 (m, 2H), 1.56-1.47 (m, 1H), 1.25 (d, J=6 Hz, 3H). MS (ESI) [M+H]+ at 308.

1. customthe resulting mixture was degassed for an additional 10 minutes
2. customsealed
3. stirringstirred at r.t. for 18 hours
4. concentrationContents were then concentrated under reduced pressure
5. dissolutionthe residue was dissolved in 100 mL dichloromethane
6. washwashed twice with each: 50 mL sat. NaHCO3, 50 mL water, and 50 mL brine
7. dry with materialdried with Na2SO4
8. concentrationconcentrated under reduced pressure
9. customThe crude material was purified by column chromatography (100% dichloromethane to 95:5 dichloromethane/methanol)
10. customto afford the product in 30% yield as a light yellow oil