O-Xylene → 5-Fluoroquinoline

HRID 910058Notes

Reaction equation

HRID 910058 reaction equation
N([O-])=O.[Na+].N[C:6]1[CH:15]=[CH:14][CH:13]=[C:12]2[C:7]=1[CH:8]=[CH:9][CH:10]=[N:11]2.C(OCC)C.C(OCC)(=O)C.C1(C)C(C)=CC=CC=1.[H+].[B-](F)(F)(F)[F:37]>>[F:37][C:6]1[CH:15]=[CH:14][CH:13]=[C:12]2[C:7]=1[CH:8]=[CH:9][CH:10]=[N:11]2

Participants

6

Reactant 5

HCID 7237O-XyleneHCID 119115-AminoquinolineHCID 28118Tetrafluoroboric acidHCID 21584169Diethylether ethylacetateHCID 23668193Sodium Nitrite

Product 1

HCID 1152435-FluoroquinolineYield 55%

Procedure

Add sodium nitrite in portions to a suspension of 5-aminoquinoline (50 g, 347 mmol) in 48% HBF4 (200 mL) at 0° C. Stir for 1 hour and then pour into 1:1 diethyl ether/ethyl acetate (500 mL). Filter the resulting suspension and dry the solid. Add this solid (82.5 g, 338 mmol) in portions to refluxing xylene (1 L), stir for 2 hours, and then cool. Decant the xylene and dissolve the residue in 1N hydrochloric acid (600 mL). Neutralize with sodium carbonate, extract with ethyl acetate (10×500 mL), dry the extracts over sodium sulfate, filter and concentrate under reduced pressure. Subject the residue to silica gel chromatography, eluting with 10-20% diethyl ether in hexanes. Combine fractions containing product and concentrate them under reduced pressure to provide the desired compound (28.1 g, 55%). MS (EL, m/z) C9H6FN (M+1) 148.0

Workup

  1. filtrationFilter the resulting suspension
  2. customdry the solid
  3. stirringstir for 2 hours
  4. temperaturecool
  5. customDecant the xylene
  6. dissolutiondissolve the residue in 1N hydrochloric acid (600 mL)
  7. extractionNeutralize with sodium carbonate, extract with ethyl acetate (10×500 mL)
  8. dry with materialdry the extracts over sodium sulfate
  9. filtrationfilter
  10. concentrationconcentrate under reduced pressure
  11. washeluting with 10-20% diethyl ether in hexanes
  12. additionCombine fractions containing product
  13. concentrationconcentrate them under reduced pressure

Sources & evidence

ORD record
ord-501ca97fc724470d86a3fcefb0021230
Source dataset
uspto-grants-2011_09
Patent number
US08022065B2

Reaction notes

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