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

HRID 876405Notes

Reaction equation

HRID 876405 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.C(OCC)(=O)C>[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

6

Reactant 3

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

Product 1

HCID 667815176-Fluoro-8-hydroxy-2-methylquinolineYield 105.1%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 8857Ethyl AcetateSolvent

Procedure

2-amino-5-fluorophenol (13.0 g, 102 mmol) was dissolved in 6N HCl (78 mL) and heated to reflux. The solution was treated with (E)-but-2-enal (8.8 mL, 107 mmol) in 1 mL portions over 1 hour. The reaction was heated at reflux for 13 hours. The reaction mixture was cooled and adjusted to pH 8 with concentrated NH4OH. The reaction was diluted with ethyl acetate, stirred for 30 minutes then filtered through a nylon membrane (0.45 μM). The filtrate was separated and the aqueous was washed with ethyl acetate then the combined organics were washed with saturated NaHCO3, saturated NaCl, dried over Na2SO4 and concentrated in vacuo to provide the product as a thick dark oil (19 g). MS APCI (+) m/z 178.1 (M+1) detected.

Workup

  1. temperatureheated to reflux
  2. temperatureThe reaction was heated
  3. temperatureat reflux for 13 hours
  4. temperatureThe reaction mixture was cooled
  5. filtrationthen filtered through a nylon membrane (0.45 μM)
  6. customThe filtrate was separated
  7. washthe aqueous was washed with ethyl acetate
  8. washthe combined organics were washed with saturated NaHCO3, saturated NaCl
  9. dry with materialdried over Na2SO4
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-47469be047d14bc4a2c897889ee8633d
Source dataset
uspto-grants-2015_03
Patent number
US08987251B2

Reaction notes

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