Sulfuric Acid → 8-Fluoro-4-methylquinoline

HRID 902016Notes

Reaction equation

HRID 902016 reaction equation
OS(O)(=O)=O.[F:6][C:7]1[CH:13]=[CH:12][CH:11]=[CH:10][C:8]=1[NH2:9].[CH:14]([C:16]([CH3:18])=O)=[CH2:15]>O1CCOCC1>[F:6][C:7]1[CH:13]=[CH:12][CH:11]=[C:10]2[C:8]=1[N:9]=[CH:15][CH:14]=[C:16]2[CH3:18]

Participants

5

Reactant 3

HCID 1118Sulfuric AcidHCID 6570Methyl vinyl ketoneHCID 95842-Fluoroaniline

Product 1

HCID 167342108-Fluoro-4-methylquinolineYield 41.4%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Procedure

Add H2SO4 (14.4 mL, 270 mmol) to a solution of 2-fluoroaniline (20.0 g, 180 mmol) in 1,4-dioxane (1 L) at room temperature. Heat the mixture to reflux and add methyl vinyl ketone (19.5 mL, 270 mmol) in 1,4-dioxane (50 mL) dropwise over 3 hours. Continue to heat for 1 hour after the addition, then remove the solvent under vacuum. Dissolve the residue in water (100 mL), neutralize with Na2CO3 and extract with CH2Cl2. Wash the combined organic extracts with water and brine, dry with anhydrous Na2SO4 and filter the mixture. Concentrate the filtrate; chromatograph the residue with silica gel (elute with 20% EtOAc in hexanes) to give the title compound 12 g (41%) as a yellowish solid.

Workup

  1. temperatureHeat the mixture
  2. temperatureto reflux
  3. temperatureContinue to heat for 1 hour
  4. additionafter the addition
  5. customremove the solvent under vacuum
  6. dissolutionDissolve the residue in water (100 mL)
  7. extractionextract with CH2Cl2
  8. washWash the combined organic extracts with water and brine
  9. dry with materialdry with anhydrous Na2SO4
  10. filtrationfilter the mixture
  11. concentrationConcentrate the filtrate

Sources & evidence

ORD record
ord-a7940962a9a44cc6babb894eb7d7a0e3
Source dataset
uspto-grants-2008_04
Patent number
US07365066B2

Reaction notes

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