Glycerol → 5-Bromo-8-fluoroquinoline

HRID 2090047Notes

Reaction equation

HRID 2090047 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]([F:9])=[C:6]([CH:8]=1)[NH2:7].O[CH2:11][CH:12]([CH2:14]O)O.[N+](C1C=C(S([O-])(=O)=O)C=CC=1)([O-])=O.[Na+].S(=O)(=O)(O)O>[OH-].[Na+]>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([F:9])=[C:6]2[C:8]=1[CH:11]=[CH:12][CH:14]=[N:7]2

Participants

6

Reactant 4

HCID 753GlycerolHCID 1118Sulfuric AcidHCID 31389Sodium 3-nitrobenzenesulfonateHCID 27694075-Bromo-2-fluoroaniline

Product 1

HCID 467392635-Bromo-8-fluoroquinoline

Reagents, catalysts & solvents 1

HCID 14798Sodium HydroxideSolvent

Conditions

Temperature
140 °C

Procedure

5-Bromo-2-fluoroaniline (1.0 g, 5.3 mmol) was mixed with glycerol (2.0 mL, 27 mmol), sodium 3-nitrobenzene sulfonate (1.2 g, 5.3 mmol) and concentrated sulfuric acid (8 mL), then the mixture was heated to 140° C. for 2 hours. The inital suspension became a dark brown solution. The mixture was allowed to cool to room temperature. The solution was made basic with 5N NaOH (30 mL), then extracted with EtOAc. The combined organic phase was washed with water then saturated NaCl (aq), dried over MgSO4, filtered, then concentrated to afford the title compound as a white solid. 1H NMR (500 MHz, CDCl3): δ 9.00 (d, J=4.2 Hz, H); 8.54 (d, J=8.6 Hz, 1H); 7.77 (dd, J=8.3, 4.5 Hz, 1H); 7.59 (dd, J=8.6, 4.2 Hz, 1H); 7.32 (dd, J=9.9, 8.3 Hz, 1H). LC4 1.81 min. (M+H)=226.

Workup

  1. temperatureto cool to room temperature
  2. extractionextracted with EtOAc
  3. washThe combined organic phase was washed with water
  4. dry with materialsaturated NaCl (aq), dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-46ac6b14af704312aeb903aa8cc8b99b
Source dataset
uspto-grants-2013_05
Patent number
US08436015B2

Reaction notes

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