Reaktion #72969

Reaktionsgleichung

ethyl 4-hydroxy-4-{[(3-nitroquinolin-4-yl)amino]methyl}piperidine-1-carboxylate

triethylamine

ethoxyacetyl chloride

→

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

Ausbeute 61.0%

Lösungsmittel

ethanol

Reaktionsbedingungen

Aufarbeitung

1. 1
   FiltrationThe mixture was filtered through CELITE
2. 2
   Filtrationfilter agent
3. 3
   Einengenthe filtrate was concentrated
4. 4
   EinengenThe residue was concentrated twice from toluene and once from chloroform
5. 5
   Sonstigeto remove the ethanol
6. 6
   workup.DISSOLUTIONwas dissolved in dichloromethane (100 mL)
7. 7
   workup.WAITAfter 1 h at rt
8. 8
   Einengenthe solution was concentrated to a yellow foam and ethanol (120 mL) and triethylamine (6 mL)
9. 9
   workup.ADDITIONwere added
10. 10
    TemperaturThe resulting solution was heated
11. 11
    Temperaturat reflux for 16 h
12. 12
    Einengenconcentrated in vacuo
13. 13
    SonstigeThe residue was partitioned between dichloromethane and water
14. 14
    WaschenThe organic layer was washed twice with brine
15. 15
    Trocknendried over MgSO4
16. 16
    Filtrationfiltered
17. 17
    Einengenconcentrated to a crude yellow oil
18. 18
    SonstigeThe oil was purified by flash chromatography (silica gel, gradient elution with 2-7% methanol/dichloromethane)

Vorschrift

A mixture of ethyl 4-hydroxy-4-{[(3-nitroquinolin-4-yl)amino]methyl}piperidine-1-carboxylate (4.53 g, 12.1 mmol) and 5% platinum on carbon (0.50 g) in ethanol was hydrogenated on a Parr apparatus at 40 psi (2.8×105 Pa) for 2.5 h. The mixture was filtered through CELITE filter agent and the filtrate was concentrated. The residue was concentrated twice from toluene and once from chloroform to remove the ethanol, then was dissolved in dichloromethane (100 mL). To the solution at 0° C. was added triethylamine (1.86 mL, 13.3 mmol) and ethoxyacetyl chloride (88%, 1.77 g, 12.7 mmol). After 1 h at rt, the solution was concentrated to a yellow foam and ethanol (120 mL) and triethylamine (6 mL) were added. The resulting solution was heated at reflux for 16 h and then concentrated in vacuo. The residue was partitioned between dichloromethane and water. The organic layer was washed twice with brine, dried over MgSO4, filtered, and concentrated to a crude yellow oil. The oil was purified by flash chromatography (silica gel, gradient elution with 2-7% methanol/dichloromethane) to provide ethyl 4-{[2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl]methyl}-4-hydroxypiperidine-1-carboxylate as a yellow foam (3.04 g, 61%).

Quelle