Реакция #4137

Уравнение реакции

maleic acid

N-methylpiperazine

N-methylpiperazine

phenylchloroformate

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

triethylamine

→

product

Выход 61.0%

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

Выход 61.0%

Растворители

Water

ethanol

dichloromethane

dichloromethane

dichloromethane

Условия реакции

Обработка

1. 1
   Другоеthe 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
   ДругоеThe layers were separated
8. 8
   Промывкаthe organic phase was washed twice with water
9. 9
   Сушкаdried over anhydrous sodium sulfate
10. 10
    Концентрированиеconcentrated
11. 11
    workup.DISSOLUTIONThe residue was dissolved in ethanol (200 ml)
12. 12
    Температураwith heating
13. 13
    ДругоеThe maleate salt was collected

Методика

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.

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