反应详情

温度

85 °C

To a solution of 1-{1-[3-(methyloxy)-4-nitrophenyl]-4-piperidinyl}piperazine (18.03 g, 56.10 mmol and 2.23 g, 6.96 mmol from separate batches) in THF was added 1-iodo-2-fluoroethane (7.38 mL, 90.79 mmol). The reaction was stirred at 85° C. overnight. The solution was transferred to a sealed tube. Upon addition of 1-iodo-2-fluoroethane (7.38 mL, 90.79 mmol), the reaction was stirred at 85° C. for an additional 5 h. The solvent was removed in vacuo and the residue was taken up in H2O and extracted with DCM (×3), dried with MgSO4, filtered and concentrated. Purification by flash chromatography provided the title compound of step D (15.94 g, 43.50 mmol, 69%) as a yellow solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.38 (qd, J=11.9, 3.7 Hz, 2H), 1.79 (d, J=10.8 Hz, 2H), 2.32-2.42 (m, J=7.0, 3.7 Hz, 9H), 2.52 (dt, JHF=28.6 Hz, J=4.9 Hz, 2H), 2.86-2.95 (m, 2H), 3.85 (s, 3H), 3.99 (d, J=13.4 Hz, 2H), 4.46 (dt, JHF=47.8 Hz, J=4.9 Hz, 2H), 6.45 (d, J=2.4 Hz, 1H), 6.54 (dd, J=9.5, 2.6 Hz, 1H), 7.82 (d, J=9.3 Hz, 1H).

1. customThe solution was transferred to a sealed tube
2. stirringthe reaction was stirred at 85° C. for an additional 5 h
3. customThe solvent was removed in vacuo
4. extractionextracted with DCM (×3)
5. dry with materialdried with MgSO4
6. filtrationfiltered
7. concentrationconcentrated
8. customPurification by flash chromatography