反应详情

To a cooled (−78° C.) solution of tert-butyl 3-oxopiperidine-1-carboxylate (5.00 grams, 25.1 mmol) in anhydrous THF (40 mL) was added lithium bis(trimethylsilyl)amide (28.9 mL, 1.0 M in THF, 28.9 mmol) dropwise. After 90 min, a solution of 2-[N,N-bis(trifluoromethylsulfonyl)amino]5-chloropyridine (10.35 g, 26.3 mmol) in THF (20 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 sat aq NaHCO3. 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 unpurified enol triflate were added 4-ethoxycarbonylphenylboronic acid (6.33 g, 32.6 mmol) and trans-dichlorobis(triphenylphosphine) palladium (II) (890 mg, 1.26 mmol). Acetonitrile (90 mL) and sodium carbonate (63 mL, 1.0 M aqueous, 63.0 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 10% EtOAc in hexanes, then 10 to 100% EtOAc) provided the title compound: LCMS m/z 276.0 [M-tBu]+; 1H NMR (500 MHz, CDCl3) δ 8.00 (d, J=8.0 Hz, 2H), 7.42 (d, J=8.0 Hz, 2H), 6.34-6.32 (m, 1H), 4.37 (q, J=7.0 Hz, 2H), 4.30-4.24 (br m, 2H), 3.58-3.54 (m, 2H), 2.34 (br m, 2H), 1.50 (s, 9H), 1.39 (t, J=7.0 Hz, 3H).

1. customwas quenched
2. additionby pouring
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 unpurified enol triflate
11. customthe resulting mixture was degassed via nitrogen
12. customsparge
13. temperatureto cool to room temperature
14. additionwas poured into water
15. extractionThe mixture was extracted with EtOAc
16. concentrationthe organic phase was concentrated in vacuo
17. customPurification by chromatography on silica gel (0 to 10% EtOAc in hexanes