Reaktion #72977

Reaktionsgleichung

tert-butyl 4-{[(3-aminoquinolin-4-yl)amino]methyl}-4-hydroxypiperidine-1-carboxylate

triethylamine

triethylamine

ethoxyacetyl chloride

→

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

Lösungsmittel

dichloromethane

Reaktionsbedingungen

Aufarbeitung

1. 1
   Einengenconcentrated in vacuo to a foam and ethanol (400 mL) and triethylamine (24 mL)
2. 2
   workup.ADDITIONwere added
3. 3
   TemperaturThe resulting solution was heated
4. 4
   Temperaturat reflux for 20 h
5. 5
   Einengenconcentrated in vacuo
6. 6
   workup.DISSOLUTIONThe residue was dissolved in dichloromethane (600 mL)
7. 7
   Waschenwashed with water (2×200 mL) and brine (2×250 mL)
8. 8
   TrocknenThe organic layer was dried twice over MgSO4
9. 9
   Filtrationfiltered
10. 10
    Einengenconcentrated to an oil
11. 11
    SonstigeThe oil was purified twice by flash chromatography (silica gel, gradient elution with 3-5% methanol/dichloromethane)

Vorschrift

To a solution of tert-butyl 4-{[(3-aminoquinolin-4-yl)amino]methyl}-4-hydroxypiperidine-1-carboxylate (50.3 mmol, prepared as described above) in dichloromethane (330 mL) at 0° C. was added triethylamine (8 mL, 57.4 mmol) followed by dropwise addition of ethoxyacetyl chloride (88%, 6.59 g, 50.3 mmol). After 3 h at rt, more triethylamine (4 mL) and acid chloride (1.70 g) were added. The solution was stirred 1 h, then concentrated in vacuo to a foam and ethanol (400 mL) and triethylamine (24 mL) were added. The resulting solution was heated at reflux for 20 h and then concentrated in vacuo. The residue was dissolved in dichloromethane (600 mL) and washed with water (2×200 mL) and brine (2×250 mL). The organic layer was dried twice over MgSO4, filtered, and concentrated to an oil. The oil was purified twice by flash chromatography (silica gel, gradient elution with 3-5% methanol/dichloromethane) to provide tert-butyl 4-{[2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl]methyl}-4-hydroxypiperidine-1-carboxylate as a yellow foam containing dichloromethane (13.13 g). Based on 1H NMR integration, the calculated amount of product was 12.59 g (57%).

Quelle