Methanol → Quinoline, 2,6-dimethoxy-4-methyl-

HRID 1018026Notes

Reaction equation

HRID 1018026 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[N:9]=[C:8](Cl)[CH:7]=[C:6]2[CH3:14].[CH3:15][OH:16].C[O-].[Na+]>O>[CH3:15][O:16][C:8]1[CH:7]=[C:6]([CH3:14])[C:5]2[C:10](=[CH:11][CH:12]=[C:3]([O:2][CH3:1])[CH:4]=2)[N:9]=1

Participants

5

Reactant 3

HCID 887MethanolHCID 2247882-Chloro-6-methoxy-4-methylquinolineHCID 10942334Sodium Methoxide2×

Product 1

HCID 12471394Quinoline, 2,6-dimethoxy-4-methyl-

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
60 °C

Procedure

A 1-liter, four-necked round bottom flask equipped with a mechanical stirrer, condenser, thermowatch and addition funnel was charged with 6-methoxy-4-methyl-2-chloroquinoline (3) (20.75 g, 0.1 moles) and methanol (250 ml). Methanolic sodium methoxide (25%, 108 g, 0.5 moles) was added over 15 minutes. The resulting mixture was heated to reflux and held for 24 hours. Additional methanolic sodium methoxide was added (25%, 42 g, 0.2 moles) and the reaction was refluxed an additional 21 hours. The mixture was cooled to 60° C. and water (200 ml) was added slowly. The slurry was cooled to 10° C., the product isolated by suction filtration, washed with water, and air dried. Yield was 17.9 g (88.2%); mp=58-59° C.; purity by HPLC=100 area %.

Workup

  1. customA 1-liter, four-necked round bottom flask equipped with a mechanical stirrer, condenser
  2. additionthermowatch and addition funnel
  3. temperatureThe resulting mixture was heated
  4. temperatureto reflux
  5. temperaturethe reaction was refluxed an additional 21 hours
  6. temperatureThe slurry was cooled to 10° C.
  7. customthe product isolated by suction filtration
  8. washwashed with water, and air
  9. customdried

Sources & evidence

ORD record
ord-5f12fb37c3094a749ea371777397a9b5
Source dataset
uspto-grants-2002_11
Patent number
US06479660B1

Reaction notes

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