反応 #1193494

反応方程式

p-chlorofluorobenzene

1-methyl-3-phenyl-4-piperidinol

DMF

DMF

sodium hydride

→

trans-4-(4-chlorophenoxy)-1-methyl-3-phenylpiperidine

溶媒

benzene

benzene

benzene

dichloromethane

反応条件

後処理

1. 1
   温度The mixture is heated
2. 2
   温度to reflux
3. 3
   温度After refluxing for 1 hour
4. 4
   温度the mixture is refluxed for 5 hours
5. 5
   workup.STIRRINGstirred for 18 hours at room temperature
6. 6
   温度refluxed an additional 4 hours
7. 7
   その他The mixture is partitioned between ether and saturated aqueous NaCl solution
8. 8
   抽出The aqueous phase is extracted with ether
9. 9
   洗浄The combined extracts are washed with water, saturated aqueous NaCl solution
10. 10
    乾燥dried over anhydrous MgSO4
11. 11
    その他Removal of the solvent in vacuo
12. 12
    その他affords an oil
13. 13
    抽出extracted with 2 N HCl solution
14. 14
    洗浄The dichloromethane phase is washed with saturated aqueous NaHCO3 solution
15. 15
    乾燥dried over anhydrous MgSO4
16. 16
    ろ過filtered
17. 17
    濃縮concentrated in vacuo
18. 18
    その他to afford an oil which
19. 19
    その他crystallizes
20. 20
    その他This material is chromatographed on silica gel

実験手順

A suspension of 7.65 g of 1-methyl-3-phenyl-4-piperidinol (approximately a 50:50 mixture of isomers) of Example 1 in 100 ml of benzene is added to a suspension of 1.2 g of sodium hydride in 50 ml dry benzene. The mixture is heated to reflux, and 25 ml of dry DMF are added dropwise over a 10-minute period. After refluxing for 1 hour, the mixture is cooled to room temperature and a solution of 6.53 g of p-chlorofluorobenzene in 50 ml of benzene is added all at once. After stirring for 18 hours at room temperature, 100 ml of DMF are added and the mixture is refluxed for 5 hours, then stirred for 18 hours at room temperature and then refluxed an additional 4 hours. The mixture is partitioned between ether and saturated aqueous NaCl solution. The aqueous phase is extracted with ether. The combined extracts are washed with water, saturated aqueous NaCl solution and dried over anhydrous MgSO4. Removal of the solvent in vacuo affords an oil. This material is dissolved in dichloromethane and extracted with 2 N HCl solution. The dichloromethane phase is washed with saturated aqueous NaHCO3 solution, dried over anhydrous MgSO4, filtered and concentrated in vacuo to afford an oil which crystallizes on standing. This material is chromatographed on silica gel, using acetone and then 25% methanol/acetone as solvent. A pure product, trans-4-(4-chlorophenoxy)-1-methyl-3-phenylpiperidine, is thus obtained, m.p. s 83.5°, 84.5°-87° C.

出典