Glycerol → 6-Bromo-7-fluoroquinoline

HRID 1959622Notes

Reaction equation

HRID 1959622 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([NH2:8])=[CH:4][C:3]=1[F:9].O[CH2:11][CH:12]([CH2:14]O)O.[OH-].[NH4+]>S(=O)(=O)(O)O>[Br:1][C:2]1[CH:7]=[C:6]2[C:5](=[CH:4][C:3]=1[F:9])[N:8]=[CH:14][CH:12]=[CH:11]2

Participants

5

Reactant 3

HCID 753GlycerolHCID 14923Ammonium HydroxideHCID 8218484-Bromo-3-fluoroaniline

Product 1

HCID 145483436-Bromo-7-fluoroquinolineYield 39%

Reagents, catalysts & solvents 1

HCID 1118Sulfuric AcidSolvent

Conditions

Temperature
130 °C

Procedure

To a suspension of 4-bromo-3-fluoro-phenylamine (100.0 g, 526 mmol) in concentrated sulfuric acid (290 mL) was added glycerol (220.0 g, 2.39 mol, 4.5 eq.) followed by ferrous sulfate (30.0 g, 0.2 eq.). The reaction mixture was heated at 130° C. for 14 h, cooled to it and poured onto ice-water. The solution was adjusted with saturated aqueous ammonium hydroxide to pH 8 and extracted with DCM (2 L×3). The combined organic layers were washed with brine (1 L×3), dried over Na2SO4 and concentrated under reduced pressure to afford a crude product, which was purified by column chromatography (petroleum:EtOAc=10:1) to give the title compound as white solid (45 g, 39%). 1H-NMR (400 MHz, DMSO-d6) ppm 8.86 (s, 1H), 8.56 (m, 1H), 8.45 (m, 1H), 7.90 (d, 1H), 7.71 (m, 1H).

Workup

  1. temperaturecooled to it
  2. additionpoured onto ice-water
  3. extractionextracted with DCM (2 L×3)
  4. washThe combined organic layers were washed with brine (1 L×3)
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated under reduced pressure
  7. customto afford a crude product, which
  8. customwas purified by column chromatography (petroleum:EtOAc=10:1)

Sources & evidence

ORD record
ord-cadd190bbd7b42599f9ef7bfb4413587
Source dataset
uspto-grants-2013_04
Patent number
US08410264B2

Reaction notes

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