Reaktion #72992

Reaktionsgleichung

ethoxyacetyl chloride

ethoxyacetyl chloride

8-{[(3-aminoquinolin-4-yl)amino]methyl}-1,4-dioxaspiro[4.5]decan-8-ol

triethylamine

triethylamine

→

8-{[2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl]methyl}-1,4-dioxaspiro[4.5]decan-8-ol

Ausbeute 19.4%

Lösungsmittel

ethanol

dichloromethane

dichloromethane

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.WAITAfter two hours
2. 2
   Sonstigethe solution was transferred to a separatory funnel
3. 3
   Waschenwashed with water (200 mL)
4. 4
   TrocknenThe organic layer was dried with Na2SO4
5. 5
   Filtrationfiltered
6. 6
   Einengenconcentrated under reduced pressure
7. 7
   Sonstigeto yield an orange solid
8. 8
   TemperaturThe solution was heated
9. 9
   Temperaturat reflux for 16 h
10. 10
    SonstigeThe volatiles were removed under reduced pressure
11. 11
    Sonstigeto yield a brown oil that
12. 12
    Sonstigewas crystallized from isopropanol

Vorschrift

A solution of ethoxyacetyl chloride (4.38 g, 35.7 mmol) in dichloromethane (50 mL) was added to a 0° C. solution of 8-{[(3-aminoquinolin-4-yl)amino]methyl}-1,4-dioxaspiro[4.5]decan-8-ol (10.7 g, 32.5 mmol) and triethylamine (4.98 mL, 35.7 mmol) in dichloromethane (250 mL). After one hour, the solution was allowed to warm to rt and stir for 2 d. More ethoxyacetyl chloride (0.15 equivalent) was added. After two hours, the solution was transferred to a separatory funnel and washed with water (200 mL). The organic layer was dried with Na2SO4, filtered, and concentrated under reduced pressure to yield an orange solid. The solid was dissolved in ethanol (150 mL) and triethylamine (13.6 mL, 97.4 mmol) was added. The solution was heated at reflux for 16 h. The volatiles were removed under reduced pressure to yield a brown oil that was crystallized from isopropanol to yield 8-{[2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl]methyl}-1,4-dioxaspiro[4.5]decan-8-ol as off-white crystals (2.50 g) and a second crop (1.50 g) of crystals. A third crop (4.91 g) was isolated after recrystallization of the mother liquor from ethyl acetate. A total of 8.91 g (69%) of 8-{[2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl]methyl}-1,4-dioxaspiro[4.5]decan-8-ol was isolated.

Quelle