反应 #1507820

反应方程式

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

methanesulfonyl chloride

triethylamine

1,2,3,4-tetrahydro-3-isoquinolinecarboxylic acid methyl ester

potassium carbonate

potassium iodide

→

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

收率 76.0%

溶剂

water

dichloromethane

Water

N,N-Dimethylformamide

N,N-dimethyl-formamide

反应条件

后处理

1. 1
   其他at 0° C.
2. 2
   其他the phases were separated
3. 3
   洗涤The organic layer was washed with brine (20 ml)
4. 4
   干燥dried (MgSO4)
5. 5
   浓缩concentrated in vacuo
6. 6
   workup.DISSOLUTIONThe residue was dissolved in acetonitrile (12 ml)
7. 7
   温度The reaction mixture was heated at 82° C. for 12 h
8. 8
   温度heating
9. 9
   workup.WAITwas continued for further 16 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 product was purified by column chromatography on silica gel (80 g)

实验过程

To a solution of 3-(10,11-dihydro-5H-dibenz[b,f]azepin-5-yl)-1-propanol (1.05 g, 0.0041 mol, prepared similarly as described in example 2) in dichloromethane (40 ml) at 0° C., triethylamine (1.28 g, 0.013 mol) was added, followed by methanesulfonyl chloride (0.9 ml, 0.012 mol). After stirring for 30 minutes at 0° C., water (50 ml) was added and the phases were separated. The organic layer was washed with brine (20 ml), dried (MgSO4) and concentrated in vacuo. The residue was dissolved in acetonitrile (12 ml), and 1,2,3,4-tetrahydro-3-isoquinolinecarboxylic acid methyl ester (1.13 g, 0.0050 mol), N,N-dimethyl-formamide (5 ml), potassium carbonate (1.32 g, 0.0096 mol) and potassium iodide (0.30 g, 0.0018 mol) were added. The reaction mixture was heated at 82° C. for 12 h. N,N-Dimethylformamide (5 ml) was added and heating was continued for further 16 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 product was purified by column chromatography on silica gel (80 g) using a gradient of heptane and ethyl acetate (10:0→10:3), affording 1.4 g (76%) of 2-(3-(10,11-dihydro-5H-dibenz[b,f]azepin-5-yl)-1-propyl)-1,2,3,4-tetrahydro-3-isoquinolinecarboxylic acid methyl ester as an oil.

来源