反应详情

温度

80 °C

Thionyl chloride (52 mL, 0.716 mol) is added drop wise to a stirred solution of 2-[{4-[5-(2-fluoro-biphenyl-4-yl)-1,2,4-oxadiazole-3-yl]benzyl}(2-hydroxyethyl)-amino]ethanol (31 g, 0.0715 mol) in dichloromethane (150 mL) at 0° C. N,N-Dimethylformamide (2 mL) is added and the reaction mixture is heated at 80° C. for 1 h. Excess thionyl chloride is removed under reduced pressure and the residue is made alkaline (pH ˜9) by the addition of an aqueous sodium hydroxide solution (4N, 150 mL) at room temperature. The aqueous layer is extracted with ethyl acetate (2×100 mL) and combined organic layers are dried over sodium sulphate. Removal of solvent under reduced pressure gives a viscous liquid, which is purified by column chromatography (silica gel 230-400 mesh, n-hexane:ethyl acetate 7:3) to give bis-(2-chloroethyl){4-[5-(2-fluorobiphenyl-4-yl)-1,2,4-oxadiazole-3-yl]benzyl}amine.

1. customExcess thionyl chloride is removed under reduced pressure
2. additionby the addition of an aqueous sodium hydroxide solution (4N, 150 mL) at room temperature
3. extractionThe aqueous layer is extracted with ethyl acetate (2×100 mL)
4. dry with materialare dried over sodium sulphate
5. customRemoval of solvent under reduced pressure
6. customgives a viscous liquid, which
7. customis purified by column chromatography (silica gel 230-400 mesh, n-hexane:ethyl acetate 7:3)