Ammonium Hydroxide → 7-Methoxy-2,6-dimethylquinoline

HRID 338950Notes

Reaction equation

HRID 338950 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:7]=[CH:8][C:9]=1[CH3:10])[NH2:6].[CH:11](=O)/[CH:12]=[CH:13]/[CH3:14].[NH4+].[OH-]>Cl>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:7]([CH:11]=[CH:12][C:13]([CH3:14])=[N:6]2)=[CH:8][C:9]=1[CH3:10]

Participants

5

Reactant 3

HCID 14923Ammonium HydroxideHCID 278823-Methoxy-4-methylanilineHCID 447466Crotonaldehyde

Product 1

HCID 867074717-Methoxy-2,6-dimethylquinolineYield 42.5%

Reagents, catalysts & solvents 1

HCID 313Hydrochloric AcidSolvent

Procedure

To 3-methoxy-4-methylaniline (1.0 g, 7.29 mmol) in refluxing in 6N HCl (50 mL) was added dropwise (E)-but-2-enal (1.02 g, 14.6 mmol). The reaction was heated to reflux for 2 hours then cooled down and neutralized with NH4OH. The organic phase was extracted with DCM and the combined organic phases dried over MgSO4, filtered and concentrated under reduced pressure to leave a dark residue. The residue was purified by reverse phase chromatography (SP4, 25M, eluting with a gradient of water/ACN 100:0 to 0:100, 20 column volumes) to yield 7-methoxy-2,6-dimethylquinoline (580 mg, 29.7% yield) as a beige solid.

Workup

  1. temperatureThe reaction was heated
  2. temperatureto reflux for 2 hours
  3. temperaturethen cooled down
  4. extractionThe organic phase was extracted with DCM
  5. dry with materialthe combined organic phases dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customto leave a dark residue
  9. customThe residue was purified by reverse phase chromatography (SP4, 25M
  10. washeluting with a gradient of water/ACN 100:0 to 0:100, 20 column volumes)

Sources & evidence

ORD record
ord-d1a62e775ff14853b31c0c1618bab9fe
Source dataset
uspto-grants-2014_11
Patent number
US08889704B2

Reaction notes

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