反応 #62666

反応方程式

maleic acid

N-methylpiperazine

N-methylpiperazine

phenylchloroformate

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

triethylamine

→

product

収率 61.0%

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

収率 61.0%

溶媒

Water

ethanol

dichloromethane

dichloromethane

dichloromethane

反応条件

後処理

1. 1
   その他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
   workup.STIRRINGwith vigorous stirring The layers
8. 8
   その他were separated
9. 9
   洗浄the organic phase was washed twice with water
10. 10
    乾燥dried over anhydrous sodium sulfate
11. 11
    濃縮concentrated
12. 12
    workup.DISSOLUTIONThe residue was dissolved in ethanol (200 ml)
13. 13
    温度with heating
14. 14
    その他The maleate salt was collected

実験手順

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 methaol afforded the analytical sample, mp 172°-174° C.

出典