反应 #1363582

反应方程式

alcohol

3-(10,11-dihydro-5H-dibenz[b,f]azepin-5-yl)-1-propanol

triethylamine

methanesulfonyl chloride

mesylate

4-(4-chlorophenyl)piperidin-4-ol

potassium carbonate

→

title compound

收率 61.0%

4-(4-Chlorophenyl)-1-(3-(10,11-dihydro-5H-dibenz[b,f]azepin-5-yl)-1-propyl)piperidin-4-ol hydrochloride

收率 61.0%

溶剂

toluene

acetonitrile

Water

Water

反应条件

后处理

1. 1
   其他the phases were separated
2. 2
   萃取The aqueous phase was extracted with toluene (50 ml)
3. 3
   洗涤the combined organic phases were washed with brine (2×50 ml)
4. 4
   干燥dried (MgSO4)
5. 5
   浓缩concentrated in vacuo
6. 6
   温度heated
7. 7
   温度at reflux temperature for 6 h
8. 8
   workup.WAITThe reaction mixture was left
9. 9
   workup.STIRRINGstirring at room temperature for 2 days
10. 10
    萃取the mixture was extracted with ethyl acetate (3×15 ml)
11. 11
    洗涤washed with brine (2×20 ml)
12. 12
    干燥dried (MgSO4)
13. 13
    浓缩concentrated in vacuo
14. 14
    workup.ADDITIONWater (50 ml) was added
15. 15
    workup.ADDITIONthe mixture was acidified by addition of concentrated hydrochloric acid (3 ml)
16. 16
    萃取The aqueous solution was extracted with dichloromethane (2×20 ml)
17. 17
    洗涤washed with brine (2×20 ml)
18. 18
    干燥dried (MgSO4)
19. 19
    浓缩concentrated in vacuo
20. 20
    workup.DISSOLUTIONThe resulting oil was dissolved in a mixture of ethyl acetate (15 ml) and methanol (2 ml)
21. 21
    workup.ADDITIONHeptane was added in small portions, just until the solution
22. 22
    workup.WAITAfter 4 h
23. 23
    过滤crystals were filtered off
24. 24
    洗涤washed with heptane
25. 25
    其他dried

实验过程

To a stirred solution of the above alcohol (1.01 g, 0.004 mol) and triethylamine (1.02 g, 0.010 mol) in toluene (25 ml) at 0° C., methanesulfonyl chloride (0.6 ml, 0.0077 mol) was added dropwise over 10 minutes. The resulting mixture was stirred at 0° C. for 1.5 h. Water (50 ml) was added and the phases were separated. The aqueous phase was extracted with toluene (50 ml), and the combined organic phases were washed with brine (2×50 ml), dried (MgSO4) and concentrated in vacuo. The crude mesylate was mixed with 4-(4-chlorophenyl)piperidin-4-ol (0.81 g, 0.004 mol) and potassium carbonate (1.08 g, 0.008 mol) in acetonitrile (9 ml) and heated at reflux temperature for 6 h. The reaction mixture was left stirring at room temperature for 2 days. Water (50 ml) was added and the mixture was extracted with ethyl acetate (3×15 ml), washed with brine (2×20 ml), dried (MgSO4) and concentrated in vacuo. Water (50 ml) was added and the mixture was acidified by addition of concentrated hydrochloric acid (3 ml). The aqueous solution was extracted with dichloromethane (2×20 ml), washed with brine (2×20 ml), dried (MgSO4) and concentrated in vacuo. The resulting oil was dissolved in a mixture of ethyl acetate (15 ml) and methanol (2 ml). Heptane was added in small portions, just until the solution turned slightly turbid. After 4 h, crystals were filtered off, washed with heptane and dried, affording 1.1 g (61%) of the title compound as a solid.

来源