反应详情

To a cooled (−78° C.) solution of 1-Boc-3-pyrollidinone (8.00 grams, 43.2 mmol) in anhydrous THF (70 mL) was added lithium bis(trimethylsilyl)amide (49.7 mL, 1.0 M in THF, 49.7 mmol) dropwise. After 45 min, a solution of 2-[N,N-bis(trifluoromethylsulfonyl)amino]5-chloropyridine (17.81 g, 45.4 mmol) in THF (65 mL) was added, and the resulting mixture was allowed to warm slowly to ambient temperature overnight, at which point it was quenched by pouring into brine. The mixture was extracted with EtOAc. The organic phase was separated, dried over anhydrous sodium sulfate, and concentrated in vacuo. The resulting enol triflate was filtered though silica gel, concentrated in vacuo, and used without further purification. To a flask containing the enol triflate obtained above (4.94 g, 15.6 mmol) were added 4-ethoxycarbonylphenylboronic acid (3.32 g, 17.1 mmol) and trans-dichlorobis(triphenylphosphine) palladium (II) (1.09 g, 1.56 mmol). Acetonitrile (78 mL) and sodium carbonate (39 mL, 1.0 M aqueous, 39 mmol) were added, and the resulting mixture was degassed via nitrogen sparge. The reaction mixture was stirred at 70° C. for 3 h, then was allowed to cool to room temperature and was poured into water. The mixture was extracted with EtOAc, and the organic phase was concentrated in vacuo. Purification by chromatography on silica gel (0 to 25% EtOAc in hexanes, then 25 to 100% EtOAc in hexanes) provided the title compound: LCMS m/z 261.9 [M-t-Boc]+; 1H NMR (500 MHz, CDCl3) δ 8.03 (d, J=8.0 Hz, 2 H), 7.44 (d, J=8.5 Hz, 2H), 6.29 (ddd, J=25.0, 4, 4 Hz, 1H), 4.58-4.46 (m, 2H), 4.41-4.28 (m, 2H), 4.38 (q, J=7.0 Hz, 2H), 1.53 and 1.51 (s, doubled (rotamers) 9H), 1.40 (t, doubled (rotamers) J=7.0 Hz, 1.5H), 1.39 (t, doubled (rotamers) J=7.0 Hz, 1.5H).

1. customwas quenched
2. additionby pouring into brine
3. extractionThe mixture was extracted with EtOAc
4. customThe organic phase was separated
5. dry with materialdried over anhydrous sodium sulfate
6. concentrationconcentrated in vacuo
7. filtrationThe resulting enol triflate was filtered though silica gel
8. concentrationconcentrated in vacuo
9. customused without further purification
10. additionTo a flask containing the enol triflate
11. customobtained above (4.94 g, 15.6 mmol)
12. customthe resulting mixture was degassed via nitrogen
13. customsparge
14. temperatureto cool to room temperature
15. additionwas poured into water
16. extractionThe mixture was extracted with EtOAc
17. concentrationthe organic phase was concentrated in vacuo
18. customPurification by chromatography on silica gel (0 to 25% EtOAc in hexanes