反应 #1363584

反应方程式

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

3-piperidinecarboxamide

potassium carbonate

methanesulfonyl chloride

triethylamine

→

title compound

收率 64.0%

1-(3-(10,11-Dihydro-5H-dibenz[b,f]azepin-5-yl)-1-propyl)-3-piperidinecarboxamide hydrochloride

收率 64.0%

溶剂

Toluene

water

toluene

Water

反应条件

后处理

1. 1
   其他at 0° C.
2. 2
   其他the phases were separated
3. 3
   萃取The aqueous phase was extracted with toluene (50 ml)
4. 4
   洗涤the combined organic phases were washed with brine (2×100 ml)
5. 5
   干燥dried (MgSO4)
6. 6
   浓缩concentrated in vacuo
7. 7
   workup.DISSOLUTIONThe residue was dissolved in acetonitrile (20 ml)
8. 8
   温度The mixture was heated
9. 9
   温度at reflux temperature for 4 h
10. 10
    workup.STIRRINGstirred at room temperature for 40 h
11. 11
    萃取the product was extracted with ethyl acetate (2×20 ml)
12. 12
    洗涤The combined organic extracts were washed with brine (2×20 ml)
13. 13
    干燥dried (MgSO4)
14. 14
    浓缩concentrated in vacuo
15. 15
    workup.ADDITIONWater (20 ml) and concentrated hydrochloric acid (3.0 ml) were added
16. 16
    萃取the mixture was extracted with dichloromethane (2×20 ml)
17. 17
    干燥dried (MgSO4)
18. 18
    浓缩concentrated in vacuo
19. 19
    workup.DISSOLUTIONThe residue was redissolved in a mixture of warm ethyl acetate (10 ml) and methanol (1.0 ml)
20. 20
    workup.WAITafter standing for 5 h at room temperature
21. 21
    过滤a precipitate was filtered off
22. 22
    其他dried

实验过程

To a stirred solution of 3-(10,11-dihydro-5H-dibenz[b,f]azepin-5-yl)-1-propanol (1.44 g, 0.0057 mol, prepared similarly as described in example 2) and triethylamine (1.46 g, 0.014 mol) in toluene (40 ml) at 0° C., methanesulfonyl chloride (0.88 ml, 0.011 mol) was added dropwise over 10 minutes. The resulting mixture was stirred at 0° C. for 1.5 h. Toluene (50 ml) and water (100 ml) were added, and the phases were separated. The aqueous phase was extracted with toluene (50 ml), and the combined organic phases were washed with brine (2×100 ml), dried (MgSO4) and concentrated in vacuo. The residue was dissolved in acetonitrile (20 ml) and 3-piperidinecarboxamide (1.09 g, 0.0085 mol) and potassium carbonate (1.76 g, 0.013 mol) were added. The mixture was heated at reflux temperature for 4 h, and stirred at room temperature for 40 h. Water (20 ml) was added, and the product was extracted with ethyl acetate (2×20 ml). The combined organic extracts were washed with brine (2×20 ml), dried (MgSO4) and concentrated in vacuo. Water (20 ml) and concentrated hydrochloric acid (3.0 ml) were added, and the mixture was extracted with dichloromethane (2×20 ml), dried (MgSO4) and concentrated in vacuo. The residue was redissolved in a mixture of warm ethyl acetate (10 ml) and methanol (1.0 ml), and after standing for 5 h at room temperature, a precipitate was filtered off and dried, affording 1.56 g (64%) of the title compound.

来源