反应 #1363588

反应方程式

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

2-piperazine-carboxylic acid ethyl ester

potassium carbonate

methanesulfonyl chloride

triethylamine

→

4-(3-(10,11-dihydro-5H-dibenz[b,f]azepin-5-yl)-1-propyl)-2-piperazinecarboxylic acid ethyl ester

收率 33.0%

溶剂

toluene

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 layer 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 (10 ml)
8. 8
   温度The resulting mixture was heated
9. 9
   温度at reflux temperature for 18 h
10. 10
    萃取the mixture was extracted with ethyl acetate (3×20 ml)
11. 11
    洗涤The combined organic extracts were washed with brine (2×20 ml)
12. 12
    干燥dried (MgSO4)
13. 13
    浓缩concentrated in vacuo
14. 14
    其他The residue was purified by column chromatography on silica gel (27 g)

实验过程

To a stirred solution of 3-(10,11-dihydro-5H-dibenz[b,f]azepin-5-yl)-1-propanol (1.17 g, 0.0046 mol, prepared similarly as described in example 2) and triethylamine (1.18 g, 0.012 mol) in toluene (30 ml) at 0° C., methanesulfonyl chloride (0.70 ml, 0.009 mol) was added dropwise over 10 minutes. The resulting mixture was stirred at 0° C. for 1 h. Toluene (50 ml) and water (100 ml) were added, and the phases were separated. The aqueous layer 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 (10 ml) and the above 2-piperazine-carboxylic acid ethyl ester (1.40 g, 0.0089 mol), potassium carbonate (0.67 g, 0.0049 mol) and toluene (5 ml) were added. The resulting mixture was heated at reflux temperature for 18 h. Water (50 ml) was added, and the mixture was extracted with ethyl acetate (3×20 ml). The combined organic extracts were washed with brine (2×20 ml), dried (MgSO4) and concentrated in vacuo. The residue was purified by column chromatography on silica gel (27 g) using a gradient of methanol and ethyl acetate (5:100→20:100), affording 0.6 g (33%) of 4-(3-(10,11-dihydro-5H-dibenz[b,f]azepin-5-yl)-1-propyl)-2-piperazinecarboxylic acid ethyl ester as an oil.

来源