Diethyl Ether → 6-Fluoro-2,5-dimethylquinoline

HRID 1199129

Reaction equation

HRID 1199129 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.[CH2:14](OCC)C.C[Mg]Cl>[Ni+2].ClC(Cl)(CP(C1C=CC=CC=1)C1C=CC=CC=1)CP(C1C=CC=CC=1)C1C=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

6

Reactant 3

HCID 3283Diethyl EtherHCID 130353135-Bromo-6-fluoro-2-methylquinolineHCID 178418332HCID 178418332, compound

Product 1

HCID 198681766-Fluoro-2,5-dimethylquinoline

Reagents, catalysts & solvents 2

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

Procedure

Under a nitrogen atmosphere, 24.0 g (0.1 mole) of 5-bromo-6-fluoro-2-methylquinoline, 2.8 g (0.005 mole) of dichloro[1,3-bisdiphenylphosphinopropane] nickel (II) catalyst, and 380 ml of diethyl ether were combined. 44 ml of 3.17M methylmagnesium chloride in tetrahydrofuran was added dropwise at a rapid rate. The reaction was allowed to stir at room temperature overnight. The ether solution was decanted off into 200 ml of 3N hydrochloric acid in an ice bath, accompanied by vigorous stirring. The aqueous and organic layers were then separated. The aqueous layer was extracted with 100 ml of ethyl acetate and cooled in an ice bath, and the pH was adjusted to pH 10 with concentrated ammonium hydroxide. This was extracted twice with 100 ml of portions of ethyl acetate. The extracts were combined and washed with 30 ml of brine, dried over magnesium sulfate, and filtered and evaporated to give 14.9 g of 2,5-dimethyl-6-fluoroquinoline of 94.4% purity as determined by gas chromatography analysis.

Workup

  1. customThe ether solution was decanted off into 200 ml of 3N hydrochloric acid in an ice bath
  2. customThe aqueous and organic layers were then separated
  3. extractionThe aqueous layer was extracted with 100 ml of ethyl acetate
  4. temperaturecooled in an ice bath
  5. extractionThis was extracted twice with 100 ml of portions of ethyl acetate
  6. washwashed with 30 ml of brine
  7. dry with materialdried over magnesium sulfate
  8. filtrationfiltered
  9. customevaporated

Sources & evidence

ORD record
ord-a4fadf5416a64b4bb709ae26315bbe2f
Source dataset
uspto-grants-1990_02
Patent number
US04898945

Linked notes

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