Sodium Methoxide → 5-Bromo-8-fluoro-2-methoxyquinoline

HRID 2090048Notes

Reaction equation

HRID 2090048 reaction equation
[Br:1][C:2]1[CH:11]=[CH:10][C:9]([F:12])=[C:8]2[C:3]=1[CH:4]=[CH:5][C:6](Cl)=[N:7]2.[CH3:14][O-:15].[Na+]>CO.O>[Br:1][C:2]1[CH:11]=[CH:10][C:9]([F:12])=[C:8]2[C:3]=1[CH:4]=[CH:5][C:6]([O:15][CH3:14])=[N:7]2

Participants

5

Reactant 2

HCID 10942334Sodium MethoxideHCID 583494465-Bromo-2-chloro-8-fluoroquinoline

Product 1

HCID 673042505-Bromo-8-fluoro-2-methoxyquinoline

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Conditions

Temperature
50 °C

Procedure

To a suspension of 5-bromo-2-chloro-8-fluoroquinoline (1.08 g, 4.2 mmol) in anhydrous methanol (10 mL) at 50° C. was added NaOMe (30% w/w, 0.9 g, 5.0 mmol). The resulting mixture was stirred at 50° C. for one hour, then allowed to cool to room temperature. The mixture was diluted with water, then extracted with EtOAc. The combined organics were washed with water then saturated Nael (aq), dried over MgSO4, filtered, then concentrated. The residue was purified by silica gel chromatography eluting with 0-5% EtOAc/hexanes to afford the title compound as a white solid: 1H NMR (500 MHz, CDCl3): δ 8.33 (dd, J=9.1, 1.6 Hz, 1H); 7.55 (dd, J=8.4, 4.4 Hz, 1H); 7.22 (dd, J=10.2, 8.4 Hz, 1H); 7.04 (d, J=9.2 Hz, 1H); 4.13 (s, 4H). LC4 2.37 min. (M+H) 256.

Workup

  1. temperatureto cool to room temperature
  2. extractionextracted with EtOAc
  3. washThe combined organics were washed with water
  4. dry with materialsaturated Nael (aq), dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by silica gel chromatography
  8. washeluting with 0-5% EtOAc/hexanes

Sources & evidence

ORD record
ord-cb6aa7a2549542e6b90d17010680ef19
Source dataset
uspto-grants-2013_05
Patent number
US08436015B2

Reaction notes

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