Hydrochloric Acid → 6,8-Dimethoxyquinoline

HRID 987577Notes

Reaction equation

HRID 987577 reaction equation
[CH3:1][O:2][C:3]1[CH:9]=[C:8]([O:10][CH3:11])[CH:7]=[CH:6][C:4]=1[NH2:5].[CH:12]([CH:14]=[CH2:15])=O.Cl.[OH-].[Na+]>CCOC(C)=O>[CH3:11][O:10][C:8]1[CH:7]=[C:6]2[C:4](=[C:3]([O:2][CH3:1])[CH:9]=1)[N:5]=[CH:15][CH:14]=[CH:12]2

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 7847AcroleinHCID 14798Sodium HydroxideHCID 176522,4-Dimethoxyaniline

Product 1

HCID 180091746,8-DimethoxyquinolineYield 26%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
23 °C

Procedure

2,4-Dimethoxyaniline (20.0 g, 131 mmol), 8.70 mL (7.30 g, 131 mmol) acrolein and 500 mL 1 N HCl are refluxed for 30 min. The reaction mixture is cooled to 23° C., poured into 200 mL of vigorously stirring EtOAc, and neutralized with 10N NaOH. The resulting bi-phasic solution is stirred for 30 min and filtered through celite. The layers are separated, and the aqueous layer is extracted with 3×300 mL EtOAc. The combined organics are washed with 1×400 mL H2O, 1×400 mL brine, dried over MgSO4, filtered, and the volatiles are evaporated. Flash chromatography on SiO2, eluting with 4/1 EtOAc/hexanes containing 10% MeOH, gives 6.40 g (33.8 mmol, a 26% yield) of the title compound as an off-white solid. MS (ES) m/z 190 (MH)+.

Workup

  1. filtrationfiltered through celite
  2. customThe layers are separated
  3. extractionthe aqueous layer is extracted with 3×300 mL EtOAc
  4. washThe combined organics are washed with 1×400 mL H2O, 1×400 mL brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. customthe volatiles are evaporated
  8. washFlash chromatography on SiO2, eluting with 4/1 EtOAc/hexanes containing 10% MeOH
  9. customgives 6.40 g (33.8 mmol

Sources & evidence

ORD record
ord-459018190b7743a9838a317fe9852cee
Source dataset
uspto-grants-2003_10
Patent number
US06632824B2

Reaction notes

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