反应详情

To a solution of 7-methylquinoline (1.63 g, 11.4 mmol) in dry THF (10 mL), cooled by ice/water, is added phenyllithium (1.9M in cyclohexane/ether 70/30, 6.0 mL, 11.4 mmol) dropwise over 5 min. After 15 min, the cooling bath is removed, and the solution is stirred at rt for 5 h. The reaction is quenched by adding MeOH, and stirring is continued overnight. Water is added, the mixture is extracted with EtOAc (3×35 mL), and the combined extracts are dried over MgSO4. The drying agent is filtered off, and air is bubbled into the solution for 7 d. The solvent is evaporated; the residue is dissolved in warm (50° C.) EtOAc/hexanes and filtered warm. The filtrate is concentrated and dried in vacuo to obtain the crude title compound that is used directly for the next step. Further purification is possible by chromatography on silica gel (Jones Flashmaster, eluting with hexanes:EtOAc 3:1→2:1→1:1). 1H NMR (CDCl3, 400 MHz) 2.58 (s, 3H), 7.31 (d, J=3.7 Hz, 1H), 7.36-7.49 (m, 1H), 7.52 (t, J=8.0 Hz, 2H), 7.72 (d, J=8.2 Hz, 1H), 7.82 (d, J=8.2 Hz, 1H), 7.96 (s, 1H), 8.16 (t, J=8.0 Hz, 2H). MS (ES+): m/z 220.3 (100) [MH+]. HPLC: tR=2.7 min (Platform II, nonpolar 5 min).

1. customthe cooling bath is removed
2. customThe reaction is quenched
3. additionby adding MeOH
4. stirringstirring
5. waitis continued overnight
6. additionWater is added
7. extractionthe mixture is extracted with EtOAc (3×35 mL)
8. dry with materialthe combined extracts are dried over MgSO4
9. filtrationThe drying agent is filtered off
10. customair is bubbled into the solution for 7 d
11. customThe solvent is evaporated
12. dissolutionthe residue is dissolved
13. temperaturein warm (50° C.) EtOAc/hexanes
14. filtrationfiltered
15. temperaturewarm
16. concentrationThe filtrate is concentrated
17. customdried in vacuo