4-Benzyloxyaniline → Ammonium Hydroxide

HRID 2203545Notes

Reaction equation

HRID 2203545 reaction equation
C([O:8]C1C=C(C=CC=1)[NH2:12])C1C=CC=CC=1.C(OC1C=CC(N)=CC=1)C1C=CC=CC=1.COCCC(Cl)=O.C(OCC(Cl)=O)C.[CH3:45][O:46][CH2:47][CH2:48][C:49]1[N:50]([CH2:63][CH2:64][CH3:65])[C:51]2[C:60]3[CH:59]=[CH:58][C:57]([OH:61])=[CH:56][C:55]=3[N:54]=[CH:53][C:52]=2[N:62]=1.[CH:66]([N:69]=[C:70]=[O:71])([CH3:68])[CH3:67]>CN(C)C1C=CN=CC=1.C([O-])(=O)CCCCCCCCCCC.C([O-])(=O)CCCCCCCCCCC.C([Sn+2]CCCC)CCC.O1CCCC1>[OH-:8].[NH4+:12].[CH:66]([NH:69][C:70](=[O:71])[O:61][C:57]1[CH:58]=[CH:59][C:60]2[C:51]3[N:50]([CH2:63][CH2:64][CH3:65])[C:49]([CH2:48][CH2:47][O:46][CH3:45])=[N:62][C:52]=3[CH:53]=[N:54][C:55]=2[CH:56]=1)([CH3:68])[CH3:67]

Participants

11

Reactant 6

HCID 228604-BenzyloxyanilineHCID 61277Isopropyl isocyanateHCID 84189Ethoxyacetyl chlorideHCID 928923-BenzyloxyanilineHCID 27597283-Methoxypropanoyl chlorideHCID 136347851HCID 136347851, compound

Product 2

HCID 14923Ammonium HydroxideHCID 68971459HCID 68971459, compound

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 9809426Di-n-butyldilauryltinCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
7 °C

Procedure

The methods described in Parts A-I of Example 2 were followed using 3-benzyloxyaniline in lieu of 4-benzyloxyaniline and methoxypropionyl chloride in lieu of ethoxyacetyl chloride. 2-(2-Methoxyethyl)-1-propyl-1H-imidazo[4,5-c]quinolin-7-ol (2.0 g, 7.0 mmol), 4-(dimethylamino)pyridine (0.085 g, 0.70 mmol), and tetrahydrofuran (70 mL) were combined, and the mixture was cooled to 7° C. with an ice/water bath. Isopropyl isocyanate (0.689 mL, 7.01 mmol) was added dropwise to the mixture. After 20 minutes the cooling bath was removed and the reaction was stirred for an additional 24 hours. Analysis by HPLC indicated that no product had formed. Di-butyltin dilaurate (1 drop) was added, and the reaction was stirred at ambient temperature for 2.5 hours and then heated at reflux for 48 hours. The solvent was evaporated under reduced pressure, and the residue was dissolved in dichloromethane. The organic fraction was washed sequentially with water and brine, dried over magnesium sulfate, filtered, and concentrated under reduced pressure. Purification by column chromatography on silica gel (eluting with a chloroform:methanol:ammonium hydroxide gradient) provided 1.97 g of 2-(2-methoxyethyl)-1-propyl-1H-imidazo[4,5-c]quinolin-7-yl isopropylcarbamate as a white solid.

Workup

  1. customAfter 20 minutes the cooling bath was removed
  2. customhad formed
  3. stirringthe reaction was stirred at ambient temperature for 2.5 hours
  4. temperatureheated
  5. temperatureat reflux for 48 hours
  6. customThe solvent was evaporated under reduced pressure
  7. dissolutionthe residue was dissolved in dichloromethane
  8. washThe organic fraction was washed sequentially with water and brine
  9. dry with materialdried over magnesium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure
  12. customPurification by column chromatography on silica gel (
  13. washeluting with a chloroform

Sources & evidence

ORD record
ord-3930de949038417691fdc44aa74cc58b
Source dataset
uspto-grants-2016_06
Patent number
US09365567B2

Reaction notes

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