Reacción #4199

Ecuación de reacción

N-methylpiperazine

phenylchloroformate

phenylchloroformate

1-(4-Bromo-2-aminophenyl)-1,2,3,4-tetrahydroquinoline

triethylamine

→

product

Rendimiento 61.2%

4-Methyl-N-[5-bromo-2-(1,2,3,4-tetrahydro-1-quinolinyl)phenyl]piperazinecarboxamide

Rendimiento 61.2%

Disolventes

dichloromethane

Water

—

ice methanol

dichloromethane

dichloromethane

Condiciones de reacción

Tratamiento posterior

1. 1
   workup.ADDITIONwas added
2. 2
   workup.WAITAfter one hour
3. 3
   workup.ADDITIONwas added over 0.5 hour
4. 4
   workup.STIRRINGThe reaction mixture was stirred under nitrogen at room temperature overnight
5. 5
   workup.STIRRINGthe mixture was stirred 0.5 hour
6. 6
   OtroThe organic phase was separated
7. 7
   Lavadowashed 4 times with water
8. 8
   Secadodried over anhydrous sodium sulfate
9. 9
   Otroevaporated in a 100° C. bath in vacuo
10. 10
    workup.DISSOLUTIONThe residue was dissolved in toluene (40 ml)
11. 11
    Lavadoeluted with dichloromethane-methanol (98:2)
12. 12
    Otroevaporated

Procedimiento

1-(4-Bromo-2-aminophenyl)-1,2,3,4-tetrahydroquinoline (10.6 g, 0.035 mole) was dissolved on a steam bath in dichloromethane (150 ml). The solution was cooled to -5° C. in ice/methanol and triethylamine (5.01 g, 0.050 mole) was added in one portion, followed by a solution of phenylchloroformate (7.85 g, 0.050 mole) dissolved in dichloromethane (10 ml), dropwise over 15 minutes. The mixture was stirred 1 hour in the cold, 2 hours at room temperature, and an additional charge of phenylchloroformate (1.57 g, 0.010 mole) was added. After one hour, a solution of N-methylpiperazine (14.1 g, 0.14 mole) dissolved in dichloromethane (15 ml) was added over 0.5 hour. The reaction mixture was stirred under nitrogen at room temperature overnight. Water (100 ml) was added and the mixture was stirred 0.5 hour. The organic phase was separated, washed 4 times with water, dried over anhydrous sodium sulfate, and evaporated in a 100° C. bath in vacuo. The residue was dissolved in toluene (40 ml), adsorbed on a column of silica gel (500 g) packed in toluene and eluted with dichloromethane-methanol (98:2). The appropriate fractions were combined and evaporated to give 9.2 g (61%) of product, as an oil.

Fuente