反应详情

Aqueous sodium hydroxide (50% w/w, 10 g, 125 mmol) and tetrabutylammonium hydrogen sulfate (0.20 g) were added successively to a solution of {2-[4-(4,6-dimethyl-pyridin-2-yl)-piperazin-1-yl]-5-nitro-phenyl}-methanol (0.50 g, 1.46 mmol) in toluene (5 mL). The mixture was heated to reflux with vigorous stirring for 45 min then 4-(3-chloro-propyl)-morpholine (0.50 g, 3.00 mmol) was added and reflux continued for 28 h. The reaction mixture was cooled and the organic phase separated. The aqueous phase was extracted with ethyl acetate (3×5 mL). The organic phases were combined, washed with water and brine, dried over anhydrous sodium sulfate, filtered and concentrated under vacuum to give a residue which was purified by preparative TLC eluting with 2% methanol in chloroform to afford 4-(3-{2-[4-(4,6-dimethyl-pyridin-2-yl)-piperazin-1-yl]-5-nitro-benzyloxy}-propyl)-morpholine (550 mg, 80%) as a solid.

1. temperatureThe mixture was heated
2. temperatureto reflux
3. temperaturereflux
4. waitcontinued for 28 h
5. temperatureThe reaction mixture was cooled
6. customthe organic phase separated
7. extractionThe aqueous phase was extracted with ethyl acetate (3×5 mL)
8. washwashed with water and brine
9. dry with materialdried over anhydrous sodium sulfate
10. filtrationfiltered
11. concentrationconcentrated under vacuum
12. customto give a residue which
13. customwas purified by preparative TLC
14. washeluting with 2% methanol in chloroform