Hydrochloric Acid → 5-Bromo-6-fluoro-2-methylquinoline

HRID 2418237Notes

Reaction equation

HRID 2418237 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([CH3:12])[CH:6]=[CH:5]2.[Cl-].[Al+3].[Cl-].[Cl-].[Br:17]Br.Cl>ClCCCl.C1(C)C=CC=CC=1.[Cl-].[Zn+2].[Cl-]>[Br:17][C:3]1[C:2]([F:1])=[CH:11][CH:10]=[C:9]2[C:4]=1[CH:5]=[CH:6][C:7]([CH3:12])=[N:8]2

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 24408BromineHCID 707846-Fluoro-2-methylquinolineHCID 6451240Aluminum(III) Chloride

Product 1

HCID 130353135-Bromo-6-fluoro-2-methylquinoline

Reagents, catalysts & solvents 3

HCID 3007855ZincchlorideCatalystHCID 111,2-DichloroethaneSolvent2×HCID 1140TolueneSolvent

Procedure

A solution of 100.7 g (0.625 mole) of 6-fluoroquinaldine in 125 ml of 1,2-dichloroethane was added slowly over 30 minutes to 126.5 g (0.95 mole) of aluminum chloride in 125 ml of 1,2-dichloroethane. The mixture was heated to 70° to 80° C., and 32 ml of liquid bromine was added dropwise over 4 hours. The mixture was stirred and heated at 80° to 85° C. for 20 hours, and was then poured over 1.5 liters of ice. After stirring thoroughly, the mixture was acidified with 50 ml of concentrated hydrochloric acid. Zinc chloride (85 g) was added, and the mixture was stirred for 10 minutes. The mixture was cooled in an ice bath, and the solid product was separated by filtration and washed sequentially with cold 3N hydrochloric acid and dichloromethane. The solid was slurried in water and neutralized with concentrated ammonium hydroxide. Filtration provided a solid which was dissolved in toluene. The solution was dried over magnesium sulfate, and then evaporated to provide a residue which was recrystallized from hexane to provide 5-bromo-6 -fluoroquinaldine. The structure was confirmed by a nuclear magnetic resonance spectral analysis.

Workup

  1. temperatureThe mixture was heated to 70° to 80° C.
  2. temperatureheated at 80° to 85° C. for 20 hours
  3. stirringAfter stirring thoroughly
  4. stirringthe mixture was stirred for 10 minutes
  5. temperatureThe mixture was cooled in an ice bath
  6. customthe solid product was separated by filtration
  7. washwashed sequentially with cold 3N hydrochloric acid and dichloromethane
  8. filtrationFiltration
  9. customprovided a solid which
  10. dry with materialThe solution was dried over magnesium sulfate
  11. customevaporated
  12. customto provide a residue which
  13. customwas recrystallized from hexane

Sources & evidence

ORD record
ord-58429ec4a83849fdb05e0f3c92139ce2
Source dataset
uspto-grants-1984_09
Patent number
US04472407

Reaction notes

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