反应详情

A solution of diethyl azodicarboxylate (DEAD, 4.9 g, 28.3 mmol) in THF (50 ml) was added dropwise to a solution of 2-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]-butanol (6.9 g, 23.6 mmol), phthalimide (4.16 gm, 1.2 eq), and triphenylphosphine (7.4 g, 28.3 mmol) in THF (200 ml) at room temperature. The solution was stirred at room temperature for 24 hours. After the reaction, the solvent was stripped and the residue was stirred in ether (200 ml). The insolubles were removed by filtration. The oily residue from concentration of the ether solution was purified by two flash chromatography (SiO2, 75 g; eluted with dichloromethane, DCM, and 1-2%CH3OH in DCM) and SiO2, 100 g; eluted with DCM, 1 l; and 1%CH3OH in DCM, 1.2 l). Two close compounds were separated. The lower compound on TLC 3.66 g) was treated with HCl/ether in ethanol, and the solid salt was precipitated with hexane. Recrystallization from ethanol and isopropyl ether yielded white crystals 3.26 g, m.p. 210°-214° C. dec.

1. customAfter the reaction
2. customThe insolubles were removed by filtration
3. customThe oily residue from concentration of the ether solution was purified by two flash chromatography (SiO2, 75 g; eluted with dichloromethane, DCM, and 1-2%CH3OH in DCM) and SiO2, 100 g
4. washeluted with DCM, 1 l
5. customTwo close compounds
6. customwere separated
7. additionThe lower compound on TLC 3.66 g) was treated with HCl/ether in ethanol
8. customthe solid salt was precipitated with hexane
9. customRecrystallization from ethanol and isopropyl ether yielded white crystals 3.26 g, m.p. 210°-214° C. dec.