反应详情

温度

0 °C

1-(2-Fluoroethyl)-4-{1-[3-(methyloxy)-4-nitrophenyl]-4-piperidinyl}-2-piperazinone (0.832 g, 2.19 mmol) was dissolved in 50 mL of dioxane with stirring and cooled to 0° C. Tin(II) chloride (1.66 g, 8.76 mmol) in concentrated HCl (37%, 15.0 mL, 167 mmol) was added dropwise via pipet. The reaction was warmed to rt and stirred overnight. The reaction was quenched by the slow addition of 6N NaOH solution until the pH was greater than 10. The mixture was extracted with EtOAc, and the organic layer was washed with brine. The combined aqueous layers were extracted with EtOAc. The combined organic layers were dried over MgSO4, filtered, and concentrated in vacuo. The residue was purified by flash chromatography to afford 0.695 g (91%) of the title compound of step C. 1H NMR (400 MHz, DMSO-d6) δ 6.50-6.40 (m, 2H), 6.25 (dd, J=8.4, 2.0 Hz, 1H), 4.56 (t, J=4.9 Hz, 1H), 4.44 (t, J=4.9 Hz, 1H), 4.15 (br. s., 2H), 3.69 (s, 3H), 3.58 (t, J=4.9 Hz, 1H), 3.52 (t, J=4.9 Hz, 1H), 3.44-3.33 (m, 2H), 3.32-3.23 (m, 2H), 3.10 (s, 2H), 2.69 (t, J=5.4 Hz, 2H), 2.52-2.39 (m, 2H), 2.32-2.20 (m, 1H), 1.74-1.86 (m, 2H), 1.39-1.55 (m, 2H).

1. temperatureThe reaction was warmed to rt
2. stirringstirred overnight
3. customThe reaction was quenched by the slow addition of 6N NaOH solution until the pH was greater than 10
4. extractionThe mixture was extracted with EtOAc
5. washthe organic layer was washed with brine
6. extractionThe combined aqueous layers were extracted with EtOAc
7. dry with materialThe combined organic layers were dried over MgSO4
8. filtrationfiltered
9. concentrationconcentrated in vacuo
10. customThe residue was purified by flash chromatography