Water → 6-Fluoro-2,5-dimethylquinoline

HRID 1199124

Reaction equation

HRID 1199124 reaction equation
Br[C:2]1[C:11]([F:12])=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][C:6]([CH3:13])=[N:7]2.[CH3:14][Mg]Cl.O>[Ni+2].ClC(Cl)(CP(C1C=CC=CC=1)C1C=CC=CC=1)CP(C1C=CC=CC=1)C1C=CC=CC=1.C1(C)C=CC=CC=1.O1CCCC1>[CH3:13][C:6]1[CH:5]=[CH:4][C:3]2[C:8](=[CH:9][CH:10]=[C:11]([F:12])[C:2]=2[CH3:14])[N:7]=1

Participants

7

Reactant 3

HCID 962WaterHCID 130353135-Bromo-6-fluoro-2-methylquinolineHCID 178418332HCID 178418332, compound

Product 1

HCID 198681766-Fluoro-2,5-dimethylquinolineYield 44%

Reagents, catalysts & solvents 3

HCID 131716311dichloro[1,3-bisdiphenylphosphinopropane] nickel (II)CatalystHCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent

Procedure

Under a nitrogen atmosphere, 28.0 g (0.05 mole) of dichloro[1,3-bis(diphenylphosphino)propane] nickel (II) catalyst (prepared by the method of G. R. Van Hecke and W. DeW. Horrocks, Inorganic Chemistry, 5, 1968 (1966), incorporated herein by reference) was added to a solution of 240 g (1.0 mole) of 5-bromo-6-fluoro-2-methylquinoline in 3.8 liters of toluene. 440 ml (1.4 mole) of 3.17 molar methylmagnesium chloride in tetrahydrofuran was added rapidly to the above mixture, the resulting exotherm being controlled with an ice bath. The reaction was allowed to stir at room temperature overnight. The reaction was treated with 1 liter of water to destroy the excess Grignard reagent, and the organic layer and aqueous layers were then separated. The organic layer was extracted twice with 1 liter portions of 3N hydrochloric acid. The acid extracts were combined, extracted twice with 1 liter portions of methylene chloride, and made basic (pH>9) with ammonium hydroxide and ice. The product was collected as a tan solid (156.4 g, 0.894 mole). This material was recrystallized from 1 liter of hexane to give 77.1 g (0.44 mole) of 2,5-dimethyl-6-fluoroquinoline which was 98.7% pure as determined by gas chromatography analysis.

Workup

  1. customthe resulting exotherm being controlled with an ice bath
  2. customto destroy the excess Grignard reagent
  3. customthe organic layer and aqueous layers were then separated
  4. extractionThe organic layer was extracted twice with 1 liter portions of 3N hydrochloric acid
  5. extractionextracted twice with 1 liter portions of methylene chloride
  6. customThis material was recrystallized from 1 liter of hexane

Sources & evidence

ORD record
ord-f13e41b20f364585b8923927ccdf70f4
Source dataset
uspto-grants-1990_02
Patent number
US04898945

Linked notes

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