Reaktion #4137

Reaktionsgleichung

maleic acid

N-methylpiperazine

N-methylpiperazine

phenylchloroformate

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

triethylamine

→

product

Ausbeute 61.0%

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

Ausbeute 61.0%

Lösungsmittel

Water

ethanol

dichloromethane

dichloromethane

dichloromethane

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigethe 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
   SonstigeThe layers were separated
8. 8
   Waschenthe organic phase was washed twice with water
9. 9
   Trocknendried over anhydrous sodium sulfate
10. 10
    Einengenconcentrated
11. 11
    workup.DISSOLUTIONThe residue was dissolved in ethanol (200 ml)
12. 12
    Temperaturwith heating
13. 13
    SonstigeThe maleate salt was collected

Vorschrift

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.

Quelle