تفاعل #72969

معادلة التفاعل

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

المردود 61.0%

المذيبات

ethanol

ظروف التفاعل

المعالجة

1. 1
   ترشيحThe mixture was filtered through CELITE
2. 2
   ترشيحfilter agent
3. 3
   تركيزthe filtrate was concentrated
4. 4
   تركيزThe residue was concentrated twice from toluene and once from chloroform
5. 5
   أخرىto remove the ethanol
6. 6
   workup.DISSOLUTIONwas dissolved in dichloromethane (100 mL)
7. 7
   workup.WAITAfter 1 h at rt
8. 8
   تركيزthe solution was concentrated to a yellow foam and ethanol (120 mL) and triethylamine (6 mL)
9. 9
   workup.ADDITIONwere added
10. 10
    درجة الحرارةThe resulting solution was heated
11. 11
    درجة الحرارةat reflux for 16 h
12. 12
    تركيزconcentrated in vacuo
13. 13
    أخرىThe residue was partitioned between dichloromethane and water
14. 14
    غسيلThe organic layer was washed twice with brine
15. 15
    تجفيفdried over MgSO4
16. 16
    ترشيحfiltered
17. 17
    تركيزconcentrated to a crude yellow oil
18. 18
    أخرىThe oil was purified by flash chromatography (silica gel, gradient elution with 2-7% methanol/dichloromethane)

الإجراء التجريبي

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%).

المصدر