Glycerol → 7-Bromo-8-fluoroquinoline

HRID 1525914Notes

Reaction equation

HRID 1525914 reaction equation
[Br:1][C:2]1[C:3]([F:9])=[C:4]([CH:6]=[CH:7][CH:8]=1)[NH2:5].[N+]([C:13]1[CH:14]=C(S([O-])(=O)=O)C=C[CH:18]=1)([O-])=O.[Na+].C(O)C(O)CO.S(=O)(=O)(O)O.[OH-].[Na+]>O.ClCCl.[Cl-].[Na+].O>[Br:1][C:2]1[C:3]([F:9])=[C:4]2[C:6]([CH:18]=[CH:13][CH:14]=[N:5]2)=[CH:7][CH:8]=1

Participants

9

Reactant 5

HCID 753GlycerolHCID 1118Sulfuric AcidHCID 14798Sodium HydroxideHCID 31389Sodium 3-nitrobenzenesulfonateHCID 223418913-Bromo-2-fluoroaniline

Product 1

HCID 690814787-Bromo-8-fluoroquinolineYield 77%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
150 °C

Procedure

A 500 mL round bottom flask equipped with a stirbar and air-condenser was charged with 3-bromo-2-fluoroaniline (10.00 g, 52.6 mmol), sodium 3-nitrobenzenesulfonate (21.13 g, 94 mmol), and propane-1,2,3-triol (glycerol) (13.57 g, 147 mmol). The mixture was taken up in water (11.38 mL), carefully treated with conc. sulfuric acid (21.06 mL), and then heated to 150° C. with stirring for 2 h. The reaction was then cooled to room temperature and the flask fitted with an ice bath. The reaction mixture was carefully neutralized with 5N aq sodium hydroxide (˜180 mL). The mixture was then allowed to stir for 20 min, checked for neutral pH, and then diluted with dichloromethane (1000 mL). The entire mixture was transferred to a separatory funnel and the resulting emulsion was treated with ˜200 mL saturated brine and allowed to stand overnight to separate the layers. The organic layer was isolated and the aqueous layer was extracted with an additional quantity of dichloromethane (˜400 mL). The organics were then pooled, washed with 400 mL 1N aq sodium hydroxide solution, dried over sodium sulfate, filtered, and concentrated to a residue. The residue solidified under high vacuum to afford the title compound as a dark brown solid (9.16 g, 75% yield). MS(ES)+ m/e 225.9, 227.8 [M+H]+.

Workup

  1. customA 500 mL round bottom flask equipped with a stirbar and air-condenser
  2. temperatureThe reaction was then cooled to room temperature
  3. customthe flask fitted with an ice bath
  4. stirringto stir for 20 min
  5. customThe entire mixture was transferred to a separatory funnel
  6. waitto stand overnight
  7. customto separate the layers
  8. customThe organic layer was isolated
  9. extractionthe aqueous layer was extracted with an additional quantity of dichloromethane (˜400 mL)
  10. washwashed with 400 mL 1N aq sodium hydroxide solution
  11. dry with materialdried over sodium sulfate
  12. filtrationfiltered
  13. concentrationconcentrated to a residue

Sources & evidence

ORD record
ord-cc1fb8ca9eef424a8b31f312478b88a8
Source dataset
uspto-grants-2015_07
Patent number
US09084794B2

Reaction notes

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