반응 #938201

반응 방정식

p-chlorofluorobenzene

1-methyl-3-phenyl-4-piperidinol

DMF

DMF

sodium hydride

→

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

용매

benzene

benzene

benzene

dichloromethane

반응 조건

후처리

1. 1
   온도The mixture is heated
2. 2
   온도to reflux
3. 3
   온도After refluxing for 1 hour
4. 4
   온도the mixture is refluxed for 5 hours
5. 5
   workup.STIRRINGstirred for 18 hours at room temperature
6. 6
   온도refluxed an additional 4 hours
7. 7
   기타The mixture is partitioned between ether and saturated aqueous NaCl solution
8. 8
   추출The aqueous phase is extracted with ether
9. 9
   세척The combined extracts are washed with water, saturated aqueous NaCl solution
10. 10
    건조dried over anhydrous MgSO4
11. 11
    기타Removal of the solvent in vacuo
12. 12
    기타affords an oil
13. 13
    추출extracted with 2 N HCl solution
14. 14
    세척The dichloromethane phase is washed with saturated aqueous NaHCO3 solution
15. 15
    건조dried over anhydrous MgSO4
16. 16
    여과filtered
17. 17
    농축concentrated in vacuo
18. 18
    기타to afford an oil which
19. 19
    기타crystallizes
20. 20
    기타This material is chromatographed on silica gel

실험 절차

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.

출처