反应详情

A mixture of 4-(6-fluoro-1,2-benzisoxazol-3-yl)piperidine (3.0 g, 13.6 mmol), N-(3-chloropropyl)piperidine hydrochloride (4.05 g, 20.4 mmol), K2CO3 (6 g, 43.4 mmol), tetrabutylammonium hydrogen sulfate (phase transfer catalyst, 2.3 g) in acetonitrile (100 ml) and water (15 ml) was heated at reflux for 16 hours. The mixture was washed with brine and the layers were separated. The organic solution was concentrated. The crude product (6.4 g) was purified by flash chromatography over a silica gel column (55 g, sorbsil C-30; eluted with 2% CH3OH:0.5% DEA in DCM, 1.4 l). The oil thus purified (4.5 g) was treated with fumaric acid (1.6 g) in ethanol. The solid was collected: weight 3.1 g, m.p. 178°-181° C. Recrystallization from ethanol yielded 2.28 g of white crystals, m.p.=190°-192° C.

1. temperaturewas heated
2. temperatureat reflux for 16 hours
3. washThe mixture was washed with brine
4. customthe layers were separated
5. concentrationThe organic solution was concentrated
6. customThe crude product (6.4 g) was purified by flash chromatography over a silica gel column (55 g, sorbsil C-30; eluted with 2% CH3OH:0.5% DEA in DCM, 1.4 l)
7. customThe oil thus purified (4.5 g)
8. additionwas treated with fumaric acid (1.6 g) in ethanol
9. customThe solid was collected
10. customRecrystallization from ethanol