Reaktion #72986

Reaktionsgleichung

ethoxyacetyl chloride

triethylamine

ethoxyacetyl chloride

1-{[(3-aminoquinolin-4-yl)amino]methyl}cyclobutanol

triethylamine

chloroform

→

1-{[2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl]methyl}cyclobutanol

Ausbeute 63.0%

Lösungsmittel

dichloromethane

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.DISSOLUTIONapproximately two thirds of the starting material dissolved
2. 2
   workup.WAITAfter an additional 16 h
3. 3
   Einengenthe reaction solution was concentrated in vacuo
4. 4
   workup.ADDITIONTo the residue was added ethanol (190 mL) and triethylamine (13 mL)
5. 5
   TemperaturThe resulting solution was heated
6. 6
   Temperaturat reflux for 20 h
7. 7
   Einengenconcentrated in vacuo to a yellow solid
8. 8
   SonstigeThe solid was partitioned between dichloromethane (400 mL) and water (100 mL)
9. 9
   WaschenThe organic layer was washed with water (100 mL) and brine (100 mL)
10. 10
    TrocknenThe organic layer was dried over MgSO4
11. 11
    Filtrationfiltered
12. 12
    Einengenconcentrated
13. 13
    SonstigeThe crude product was crystallized from acetonitrile
14. 14
    Sonstigethe crystals were isolated by filtration

Vorschrift

To a mixture of 1-{[(3-aminoquinolin-4-yl)amino]methyl}cyclobutanol (23.1 mmol, prepared as described in Part D) in dichloromethane (154 mL) and triethylamine (3.54 mL, 25.4 mmol) at 0° C. was added chloroform (100 mL). The mixture was allowed to warm to rt and approximately two thirds of the starting material dissolved. To the mixture was slowly added ethoxyacetyl chloride (88%, 3.1 g, 24.3 mmol). The solution was stirred at rt for 2 h. More triethylamine (2 mL) and ethoxyacetyl chloride (88%, 1.0 g) were added. After an additional 16 h, the reaction solution was concentrated in vacuo. To the residue was added ethanol (190 mL) and triethylamine (13 mL). The resulting solution was heated at reflux for 20 h and then concentrated in vacuo to a yellow solid. The solid was partitioned between dichloromethane (400 mL) and water (100 mL). The organic layer was washed with water (100 mL) and brine (100 mL). The organic layer was dried over MgSO4, filtered, and concentrated. The crude product was crystallized from acetonitrile and the crystals were isolated by filtration to provide 1-{[2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl]methyl}cyclobutanol (4.52 g, 63%).

Quelle