Potassium Hydroxide → 6,7-Dimethoxy-4-(2-fluoro-5-hydroxy-4-methylphenoxy)quinoline

HRID 393612Notes

Reaction equation

HRID 393612 reaction equation
[OH-].[K+].Cl[C:4]1[C:13]2[C:8](=[CH:9][C:10]([O:16][CH3:17])=[C:11]([O:14][CH3:15])[CH:12]=2)[N:7]=[CH:6][CH:5]=1.[F:18][C:19]1[CH:24]=[C:23]([CH3:25])[C:22]([OH:26])=[CH:21][C:20]=1[OH:27]>>[CH3:15][O:14][C:11]1[CH:12]=[C:13]2[C:8](=[CH:9][C:10]=1[O:16][CH3:17])[N:7]=[CH:6][CH:5]=[C:4]2[O:27][C:20]1[CH:21]=[C:22]([OH:26])[C:23]([CH3:25])=[CH:24][C:19]=1[F:18]

Participants

4

Reactant 3

HCID 14797Potassium HydroxideHCID 4596104-Chloro-6,7-dimethoxyquinolineHCID 226465752-Fluoro-5-hydroxy-4-methylphenol

Product 1

HCID 226465836,7-Dimethoxy-4-(2-fluoro-5-hydroxy-4-methylphenoxy)quinolineYield 22.2%

Conditions

Temperature
130 °C

Procedure

Powdered potassium hydroxide (55 mg, 0.98 mmol) followed by 4-chloro-6,7-dimethoxyquinoline (200 mg, 0.89 mmol), (prepared as described for the starting material in Example 2), was added to 2-fluoro-5-hydroxy-4-methylphenol (600 mg, 4.2 mmol) heated at 130° C. and the mixture then stirred for 1.5 hours at 145° C. The mixture was allowed to cool then partitioned between ethyl acetate and water and the aqueous layer was adjusted to pH7 with 5M hydrochloric acid. The organic layer was separated, washed with brine, dried (MgSO4) and the solvent removed by evaporation. The residue was purified by preparative reverse-phase HPLC eluting with water/methanol (90/10 to 30/o) to give 6,7-dimethoxy-4-(2-fluoro-5-hydroxy-4-methylphenoxy)quinoline (65 mg, 22%) as a white solid.

Workup

  1. custom(prepared
  2. temperatureto cool
  3. customthen partitioned between ethyl acetate and water
  4. customThe organic layer was separated
  5. washwashed with brine
  6. dry with materialdried (MgSO4)
  7. customthe solvent removed by evaporation
  8. customThe residue was purified by preparative reverse-phase
  9. washHPLC eluting with water/methanol (90/10 to 30/o)

Sources & evidence

ORD record
ord-808a65988ef9499c80041eae340164f2
Source dataset
uspto-grants-2004_10
Patent number
US06809097B1

Reaction notes

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