反应详情

Combine 1-benzoyl-3-(3,4-dimethoxy-phenyl)-3-(2-methanesulfonyl-ethyl)-pyrrolidine (0.48 g, 1.1 mmol) and 4-[1-(4-fluoro-benzyl)-1 H-benzoimidazol-2-yl]-4-hydroxy-piperidine (0.54 g, 1.7 mmol), and sodium bicarbonate (0.235 g, 2.22 mmol) in tetrahydrofuran/water (15/4) (50 mL). Heat to reflux. After 72 hours, cool to ambient temperature and evaporate in vacuo to obtain a residue. Partition the residue between dichloromethane and 5% sodium bicarbonate solution. Dry the organic layer over Na2SO4, filter, and concentrate in vacuo to obtain a residue. Chromatograph the residue on silica gel eluting with 5/1 ethyl acetate/methanol to give a solid. Combine the solid with dichloromethane and extract with 5% sodium bicarbonate solution. Dry the organic layer over Na2SO4, filter, and concentrate in vacuo to obtain a solid residue. Dry the residue in vacuo at 82° C. to give the title compound: Rf=0.32 (silica gel, 5/1 ethyl acetate/methanol); mp; 111-114° C. HRMS (FAB+): calculated 663.334502. Found 663.334660.

1. temperatureHeat to reflux
2. customevaporate in vacuo
3. customto obtain a residue
4. customPartition the residue between dichloromethane and 5% sodium bicarbonate solution
5. dry with materialDry the organic layer over Na2SO4
6. filtrationfilter
7. concentrationconcentrate in vacuo
8. customto obtain a residue
9. extractionextract with 5% sodium bicarbonate solution
10. dry with materialDry the organic layer over Na2SO4
11. filtrationfilter
12. concentrationconcentrate in vacuo
13. customto obtain a solid residue
14. customDry the residue in vacuo at 82° C.