Ammonium Hydroxide → 6-Fluoro-8-hydroxy-2-methylquinoline

HRID 338885Notes

Reaction equation

HRID 338885 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[OH:9].[CH:10](=O)/[CH:11]=[CH:12]/[CH3:13].[NH4+].[OH-]>Cl>[F:8][C:5]1[CH:6]=[C:7]2[C:2](=[C:3]([OH:9])[CH:4]=1)[N:1]=[C:12]([CH3:13])[CH:11]=[CH:10]2

Participants

5

Reactant 3

HCID 14923Ammonium HydroxideHCID 1857632-Amino-5-fluorophenolHCID 447466Crotonaldehyde

Product 1

HCID 667815176-Fluoro-8-hydroxy-2-methylquinolineYield 82.5%

Reagents, catalysts & solvents 1

HCID 313Hydrochloric AcidSolvent

Procedure

To 2-amino-5-fluorophenol (5.0 g, 39 mmol) in refluxing 6N HCl (50 mL) was added dropwise over 10 minutes (E)-but-2-enal (5.5 g, 79 mmol). The reaction was heated to reflux for 3 hours then cooled down and neutralized (pH=7-8) by addition of NH4OH. The aqueous phase was extracted with DCM. The combined organic phases were dried over MgSO4, filtered and concentrated to yield 6-fluoro-2-methylquinolin-8-ol (5.7 g, 82% yield) as a dark oil which solidified upon standing.

Workup

  1. temperatureThe reaction was heated
  2. temperatureto reflux for 3 hours
  3. temperaturethen cooled down
  4. extractionThe aqueous phase was extracted with DCM
  5. dry with materialThe combined organic phases were dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-cd89c3f0e93f45d099cfa672b32c363c
Source dataset
uspto-grants-2014_11
Patent number
US08889704B2

Reaction notes

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