Glycerol → 7-Bromo-5-fluoroquinoline

HRID 1519861Notes

Reaction equation

HRID 1519861 reaction equation
Cl.[Br:2][C:3]1[CH:4]=[C:5]([CH:7]=[C:8]([F:10])[CH:9]=1)[NH2:6].O[CH2:12][CH:13]([CH2:15]O)O.[N+]([C:20]1[CH:25]=CC=C[CH:21]=1)([O-])=O.S(=O)(=O)(O)O>O.O.O.O.O.O.O.S([O-])([O-])(=O)=O.[Fe+2]>[Br:2][C:3]1[CH:9]=[C:8]([F:10])[CH:7]=[C:5]2[C:4]=1[CH:12]=[CH:13][CH:15]=[N:6]2.[Br:2][C:3]1[CH:4]=[C:5]2[C:7]([CH:21]=[CH:20][CH:25]=[N:6]2)=[C:8]([F:10])[CH:9]=1

Participants

7

Reactant 4

HCID 753GlycerolHCID 1118Sulfuric AcidHCID 7416NitrobenzeneHCID 467380753-Bromo-5-fluoroaniline hydrochloride

Product 2

HCID 666003857-Bromo-5-fluoroquinolineYield 30%HCID 687552215-Bromo-7-fluoroquinoline

Reagents, catalysts & solvents 1

HCID 62662Ferrous sulfate heptahydrateCatalyst

Procedure

To 3-bromo-5-fluoroaniline hydrochloride (2.9 g, 12.89 mmol) was added glycerol (1.9 mL, 25.99 mmol), nitrobenzene (1.3 mL), sulfuric acid (3.5 mL) and iron (II) sulfate heptahydrate (0.23 g, 0.82 mmol). The reaction mixture was placed in an oil bath set at 80° C. and stirred overnight followed by basification with 12N NaOH and extraction with dichloromethane. The organic phase was collected, dried (sodium sulfate), filtered and concentrated under reduced pressure. Purification by flash chromatography (silica, 50:50 ethyl acetate/hexane) gave 5-bromo-7-fluoroquinoline and 7-bromo-5-fluoroquinoline (1.03 g, 30%) Retention time (min)=1.877 and 1.967, method [4], MS(ESI) 227.9 (M+H).

Workup

  1. customThe reaction mixture was placed in an oil bath
  2. customset at 80° C.
  3. extractionfollowed by basification with 12N NaOH and extraction with dichloromethane
  4. customThe organic phase was collected
  5. dry with materialdried (sodium sulfate)
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customPurification by flash chromatography (silica, 50:50 ethyl acetate/hexane)

Sources & evidence

ORD record
ord-8b1919d2fd9e4d28bd62be0063475a07
Source dataset
uspto-grants-2015_07
Patent number
US09073891B2

Reaction notes

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