Iodine → 4,6-Dichloro-2-(4-fluorophenyl)quinoline

HRID 638291Notes

Reaction equation

HRID 638291 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][CH:3]=1.C([Li])CCC.[Cl:14][C:15]1[C:24]2[C:19](=[CH:20][CH:21]=[C:22]([Cl:25])[CH:23]=2)[N:18]=[CH:17][CH:16]=1.II.[OH-].[Na+]>CCOCC.CCCCCC.O1CCCC1.O>[Cl:14][C:15]1[C:24]2[C:19](=[CH:20][CH:21]=[C:22]([Cl:25])[CH:23]=2)[N:18]=[C:17]([C:2]2[CH:7]=[CH:6][C:5]([F:8])=[CH:4][CH:3]=2)[CH:16]=1

Participants

10

Reactant 5

HCID 807IodineHCID 99931-Bromo-4-fluorobenzeneHCID 14798Sodium HydroxideHCID 9360754,6-DichloroquinolineHCID 178418339Butyllithium

Product 1

HCID 136039014,6-Dichloro-2-(4-fluorophenyl)quinolineYield 48.8%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolventHCID 8058HexaneSolvent

Procedure

To a solution of 5.5 ml (50 mmol) of 1-bromo-4-fluorobenzene in 70 ml of ether cooled to -40° was added 21 ml of a 2.4M solution of butyl lithium in hexane while maintaining the temperature below -15°. This mixture was stirred at -15° for 15 min. A solution of 7.42 g (40 mmol) of 4,6-dichloroquinoline in 40 ml of tetrahydrofuran was added while maintaining the temperature at -20°. It was allowed to warm to 0° during 15 min. To the reaction mixture was then added 10 ml of water and 10.16 g (40 mmol) of iodine, and 15 ml of 3N sodium hydroxide. After 10 min of stirring this mixture was then cooled to 5°, and the solid collected. This solid was dissolved in methylene chloride, and the solution filtered through a plug of alumina. The filtrate was concentrated in vacuo to leave a residue which was crystallized from ethyl acetate to give 5.7g of crude product, mp 150°-156°.

Workup

  1. temperaturewhile maintaining the temperature below -15°
  2. temperaturewhile maintaining the temperature at -20°
  3. temperatureto warm to 0° during 15 min
  4. stirringAfter 10 min of stirring this mixture
  5. temperaturewas then cooled to 5°
  6. customthe solid collected
  7. dissolutionThis solid was dissolved in methylene chloride
  8. filtrationthe solution filtered through a plug of alumina
  9. concentrationThe filtrate was concentrated in vacuo
  10. customto leave a residue which
  11. customwas crystallized from ethyl acetate

Sources & evidence

ORD record
ord-8a4b8dbe5c3541e0986c05d4ac58ebea
Source dataset
uspto-grants-1985_12
Patent number
US04560692

Reaction notes

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