反应详情

温度

25 °C

To a 2-neck, 2-L round bottom flask containing anhydrous EtOH (800 mL) and equipped with a mechanical stirrer and condenser was added acetyl chloride (20.2 mL, 0.267 mol, 1.1 equiv). The solution was stirred for 0.5 h and homopiperazine (24.3 g, 0.243 mol) was added, The mixture was heated to reflux for 2 h. The reaction mixture was cooled to 25° C., 4-(methylsulfonyl)benzyl chloride (25 g, 0.122 mol, 0.5 equiv) was added and the reaction mixture heated to reflux for 16 h. The reaction mixture was cooled to 25° C. and the solvent was removed under vacuum. The residue was diluted with EtOAc (500 mL) and was washed with 2N KOH (2×500 mL). The aqueous layer was extracted with EtOAc (1×500 mL). The organic phase was combined, washed with 2N KOH (1×300 mL), dried (MgSO4) and concentrated. The crude solid was washed with hot EtOAc to yield pure desired product (8.03 g, 32.7 g theoretical, 25%) as an off-white solid, TLC R1 0.04 (10% CH3OH—CH2Cl2); 1H NMR (CDCl3, 300 MHz) δ 9.82 (br s, 1H), 7.92 (d, J=8.0 Hz, 2H), 7.60 (d, J=7.7 Hz, 2H), 3.80 (br s, 2H), 3.36 (br m, 2H), 3.07 (s, 3H), 2.93 (br s, 2H), 2.80 (br s, 2H), 2.12 (br m, 2H).

1. customequipped with a mechanical stirrer and condenser
2. temperatureThe mixture was heated
3. temperatureto reflux for 2 h
4. temperaturethe reaction mixture heated
5. temperatureto reflux for 16 h
6. temperatureThe reaction mixture was cooled to 25° C.
7. customthe solvent was removed under vacuum
8. additionThe residue was diluted with EtOAc (500 mL)
9. washwas washed with 2N KOH (2×500 mL)
10. extractionThe aqueous layer was extracted with EtOAc (1×500 mL)
11. washwashed with 2N KOH (1×300 mL)
12. dry with materialdried (MgSO4)
13. concentrationconcentrated
14. washThe crude solid was washed with hot EtOAc