反应 #4195

反应方程式

maleic acid

N-methylpiperazine

N-methylpiperazine

phenylchloroformate

1-(2-aminophenyl)-6-bromo-1,2,3,4-tetrahydroquinoline

triethylamine

→

product

收率 61.0%

4-Methyl-N-[2-(6-bromo-1,2,3,4-tetrahydro-1-quinolinyl)phenyl]piperazinecarboxamide maleate

收率 61.0%

溶剂

Water

ethanol

dichloromethane

dichloromethane

dichloromethane

反应条件

后处理

1. 1
   其他the reaction temperature below 5° C
2. 2
   workup.ADDITIONThe addition
3. 3
   workup.ADDITIONwas added dropwise over a 45 minute period
4. 4
   workup.STIRRINGThe solution was stirred for 3 hours
5. 5
   workup.ADDITIONwas added
6. 6
   workup.STIRRINGthe mixture was stirred overnight
7. 7
   其他The layers were separated
8. 8
   洗涤the organic phase was washed twice with water
9. 9
   干燥dried over anhydrous sodium sulfate
10. 10
    浓缩concentrated
11. 11
    workup.DISSOLUTIONThe residue was dissolved in ethanol (200 ml)
12. 12
    温度with heating
13. 13
    其他The maleate salt was collected

实验过程

A stirred solution, under nitrogen, of 1-(2-aminophenyl)-6-bromo-1,2,3,4-tetrahydroquinoline (21.2 g, 0.070 mole) and triethylamine (10.1 g, 0.10 mole) in dichloromethane (200 ml) was cooled to 0° C. Then there was added dropwise phenylchloroformate (15.7 g, 0.10 mole) at such a rate as to keep the reaction temperature below 5° C. The addition took 30 minutes. The mixture was stirred for 1 hour at ice-bath temperature, 2 hours at room temperature, and N-methylpiperazine (28.1 g, 0.28 mole) dissolved in dichloromethane (30 ml) was added dropwise over a 45 minute period. The solution was stirred for 3 hours and an additional charge of N-methylpiperazine (14.05 g, 0.14 mole) dissolved in dichloromethane (15 ml) was added, and the mixture was stirred overnight. Water (250 ml) was added with vigorous stirring. The layers were separated and the organic phase was washed twice with water, dried over anhydrous sodium sulfate and concentrated. The residue was dissolved in ethanol (200 ml), with heating, and treated with a warm solution of maleic acid (8.93 g, 0.077 mole) in ethanol (100 ml). The maleate salt was collected to give 23.2 g (61%) of product. Recrystallization from methanol afforded the analytical sample, mp 172°-174° C.

来源