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

HRID 44691Notes

Reaction equation

HRID 44691 reaction equation
[OH:1][C:2]1([CH2:13][NH:14][C:15]2[C:24]3[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=3)[N:18]=[CH:17][C:16]=2[N+:25]([O-])=O)[CH2:7][CH2:6][N:5]([C:8]([O:10][CH2:11][CH3:12])=[O:9])[CH2:4][CH2:3]1.C(N(CC)CC)C.[CH2:35]([O:37][CH2:38][C:39](Cl)=O)[CH3:36]>[Pt].C(O)C>[CH2:35]([O:37][CH2:38][C:39]1[N:14]([CH2:13][C:2]2([OH:1])[CH2:7][CH2:6][N:5]([C:8]([O:10][CH2:11][CH3:12])=[O:9])[CH2:4][CH2:3]2)[C:15]2[C:24]3[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=3[N:18]=[CH:17][C:16]=2[N:25]=1)[CH3:36]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 84189Ethoxyacetyl chlorideHCID 57515379Ethyl 4-hydroxy-4-{[(3-nitroquinolin-4-yl)amino]methyl}piperidine-1-carboxylate

Product 1

HCID 57515380ethyl 4-{[2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl]methyl}-4-hydroxypiperidine-1-carboxylateYield 61%

Reagents, catalysts & solvents 2

HCID 23939PlatinumCatalystHCID 702EthanolSolvent

Procedure

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%).

Workup

  1. filtrationThe mixture was filtered through CELITE
  2. filtrationfilter agent
  3. concentrationthe filtrate was concentrated
  4. concentrationThe residue was concentrated twice from toluene and once from chloroform
  5. customto remove the ethanol
  6. dissolutionwas dissolved in dichloromethane (100 mL)
  7. waitAfter 1 h at rt
  8. concentrationthe solution was concentrated to a yellow foam and ethanol (120 mL) and triethylamine (6 mL)
  9. additionwere added
  10. temperatureThe resulting solution was heated
  11. temperatureat reflux for 16 h
  12. concentrationconcentrated in vacuo
  13. customThe residue was partitioned between dichloromethane and water
  14. washThe organic layer was washed twice with brine
  15. dry with materialdried over MgSO4
  16. filtrationfiltered
  17. concentrationconcentrated to a crude yellow oil
  18. customThe oil was purified by flash chromatography (silica gel, gradient elution with 2-7% methanol/dichloromethane)

Sources & evidence

ORD record
ord-09033d8195294f709c7c4e07cde29c5c
Source dataset
uspto-grants-2013_09
Patent number
US08541438B2

Reaction notes

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