4-Chloroquinoline → Quinoline, 4-ethyl-

HRID 2371376Notes

Reaction equation

HRID 2371376 reaction equation
[CH2:1]([Li])[CH2:2][CH2:3][CH3:4].Cl[C:7]1[C:16]2[C:11](=[CH:12]C=C[CH:15]=2)[N:10]=[CH:9][CH:8]=1>[Br-].C([P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)C.C(COC)OC.C1COCC1>[CH2:3]([C:2]1[C:1]2[C:9](=[CH:8][CH:7]=[CH:16][CH:15]=2)[N:10]=[CH:11][CH:12]=1)[CH3:4]

Participants

6

Reactant 2

HCID 691404-ChloroquinolineHCID 178418339Butyllithium

Product 1

HCID 87900Quinoline, 4-ethyl-Yield 64%

Reagents, catalysts & solvents 3

HCID 73727Phosphonium, ethyltriphenyl-, bromide (1:1)CatalystHCID 8028TetrahydrofuranSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

Ethyltriphenylphosphonium bromide (45.0 g, 0.122 m) was suspended in anhydrous dimethoxyethane under a nitrogen atmosphere and cooled to -30° C. n-Butyllithium (12.2 mL of a 1 molar solution in THF) was added and the reaction mixture was stirred at -30° to -40° C. for 1 hour. 4-Chloroquinoline (9.0 g, 0.055 m) was added and the suspension was slowly warmed to room temperature and allowed to stir overnight. After heating under reflux for 2-3 hours, 50-100 mL of solvent was distilled out and replaced by a solution of sodium carbonate (12.9 g) in water (60-80 mL). After refluxing for another 2-3 hours, the solvents were evaporated and the residue was partitioned between methylene chloride and aqueous HCl. The organic phase was extracted twice with HCl, and the combined aqueous phases were basified with sodium hydroxide (50:50) to pH 9-10, extracted with ether, dried, and evaporated to give an oil which was purified by HPLC on silica gel eluting with 1:1 ethyl acetate:hexane to give 5.54 g (64%) of 4-ethylquinoline.

Workup

  1. additionwas added
  2. stirringto stir overnight
  3. temperatureAfter heating
  4. temperatureunder reflux for 2-3 hours
  5. distillation50-100 mL of solvent was distilled out
  6. temperatureAfter refluxing for another 2-3 hours
  7. customthe solvents were evaporated
  8. customthe residue was partitioned between methylene chloride and aqueous HCl
  9. extractionThe organic phase was extracted twice with HCl
  10. extractionextracted with ether
  11. customdried
  12. customevaporated
  13. customto give an oil which
  14. customwas purified by HPLC on silica gel eluting with 1:1 ethyl acetate

Sources & evidence

ORD record
ord-5fe9ab4e07104501a5ea0a0dc25da95c
Source dataset
uspto-grants-1992_03
Patent number
US05093333

Reaction notes

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