Sodium Hydroxide → 3-Fluoro-7-methoxy-2-methylquinoline

HRID 454135Notes

Reaction equation

HRID 454135 reaction equation
Cl[C:2]1[C:11]([F:12])=[CH:10][C:9]2[C:4](=[CH:5][C:6]([O:13][CH3:14])=[CH:7][CH:8]=2)[N:3]=1.[CH3:15][Mg]Br.[Cl-].[NH4+].[OH-].[Na+]>C1COCC1.[Cu]Br>[F:12][C:11]1[C:2]([CH3:15])=[N:3][C:4]2[C:9]([CH:10]=1)=[CH:8][CH:7]=[C:6]([O:13][CH3:14])[CH:5]=2

Participants

7

Reactant 4

HCID 14798Sodium HydroxideHCID 25517Ammonium ChlorideHCID 220305912-Chloro-3-fluoro-7-methoxyquinolineHCID 178418573HCID 178418573, compound

Product 1

HCID 220307923-Fluoro-7-methoxy-2-methylquinolineYield 91%

Reagents, catalysts & solvents 2

HCID 24593copper(I) bromideCatalystHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

2-Chloro-3-fluoro-7-methoxyquinoline (210 g, 1 mmol), (prepared as described for the starting material in Example 157), in anhydrous THF (1 ml) was added to a mixture of copper(I)bromide (570 mg, 4.0 mmol) and methylmagnesium bromide (3.0M solution in diethyl ether, 2.7 ml, 8 mmol) in anhydrous THF (20 ml) at −78° C. The mixture was stirred for 1 hour at −78° C., allowed to warm to ambient temperature and then stirred for a further 18 hours. Saturated aqueous ammonium chloride solution and 5N aqueous sodium hydroxide solution (pH 12) were added and the product extracted with ethyl acetate (3×). The organic solution was washed with water, brine, dried (MgSO4) and evaporated to dryness to yield 3-fluoro-7-methoxy-2-methylquinoline (0.17 g, 91%).

Workup

  1. temperatureto warm to ambient temperature
  2. stirringstirred for a further 18 hours
  3. extractionthe product extracted with ethyl acetate (3×)
  4. washThe organic solution was washed with water, brine
  5. dry with materialdried (MgSO4)
  6. customevaporated to dryness

Sources & evidence

ORD record
ord-ed7068db105d4f9788a278b38ebf3778
Source dataset
uspto-grants-2013_07
Patent number
US08492560B2

Reaction notes

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