反应详情

To a suspension of magnesium metal (4.15 g, 170.5 mmol) in anhydrous THF (40 ml) is added 1,2-dibromoethane (1.53 g, 8.12 mmol) and the mixture warmed gently. To the reaction mixture is added a solution of 1-chloromethyl-4-fluoro-benzene (23.5 g, 162.4 mmol) in THF (20 ml) dropwise over 1.5 hours. The reaction mixture is cooled to RT and stirred for 0.5 hours followed by cooling to −10° C. and addition of a solution of 1-benzyl-piperidin-4-one (9.19 g, 48.6 mmol) in THF (20 ml) dropwise over 0.5 hours. During the addition the reaction temperature is maintained below 0° C. After addition is complete the reaction is allowed to reach RT and stirred for 4 days. The resultant suspension is cooled in ice, treated with saturated ammonium chloride, stirred for 0.3 hours, treated with water and the mixture extracted with ethyl acetate. The ethyl acetate is dried with magnesium sulphate and evaporated. The crude product is purified by flash silica chromatography (methanol:dichloromethane: anmuoniumhydroxide, 1:100:0.5 elution) to afford 1-benzyl-4-(4-fluoro-benzyl)-piperidin-4-ol [MH]+ 300.8

1. temperaturethe mixture warmed gently
2. temperatureby cooling to −10° C.
3. additionDuring the addition the reaction temperature
4. temperatureis maintained below 0° C
5. additionAfter addition
6. customto reach RT
7. stirringstirred for 4 days
8. stirringstirred for 0.3 hours
9. extractionthe mixture extracted with ethyl acetate
10. dry with materialThe ethyl acetate is dried with magnesium sulphate
11. customevaporated
12. customThe crude product is purified by flash silica chromatography (methanol:dichloromethane: anmuoniumhydroxide, 1:100:0.5 elution)