3-Bromopyridine → 2-Methoxy-8-methyl-6-(3-pyridyl)quinoline

HRID 986000Notes

Reaction equation

HRID 986000 reaction equation
C([Li])(C)(C)C.Br[C:7]1[CH:8]=[C:9]2[C:14](=[C:15]([CH3:17])[CH:16]=1)[N:13]=[C:12]([O:18][CH3:19])[CH:11]=[CH:10]2.Br[C:21]1[CH:22]=[N:23][CH:24]=[CH:25][CH:26]=1>CCCCC.C1COCC1.[Cl-].[Zn+2].[Cl-].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Pd]>[CH3:19][O:18][C:12]1[CH:11]=[CH:10][C:9]2[C:14](=[C:15]([CH3:17])[CH:16]=[C:7]([C:21]3[CH:22]=[N:23][CH:24]=[CH:25][CH:26]=3)[CH:8]=2)[N:13]=1

Participants

8

Reactant 3

HCID 122863-BromopyridineHCID 14220967HCID 14220967, compoundHCID 178418306HCID 178418306, compound

Product 1

HCID 142209862-Methoxy-8-methyl-6-(3-pyridyl)quinoline

Reagents, catalysts & solvents 4

HCID 3007855ZincchlorideCatalystHCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 8003PentaneSolventHCID 8028TetrahydrofuranSolvent3×

Procedure

t-Butyl lithium (8.0 cm3 of a 2.0M solution in pentane) was added dropwise to a stirred solution of 6-bromo-2-methoxy-8 -methylquinoline (2.0 g) in THF (20 cm3) at -70° under nitrogen. After 10 minutes the mixtures was treated with a solution of anhydrous zinc chloride (1.09 g) in THF (10 cm3) and the resulting solution was warmed to 0°. A solution containing 3-bromopyridine (1.26 g) and tetrakis(triphenylphosphine) palladium(O) (0.05 g) in THF (10 cm3) was then added and the mixture was heated under reflux for 2 hours. The reaction mixture was cooled, concentrated in vacuo, treated with chloroform (100 cm3) and a solution of ethylenediaminetetraacetic acid disodium salt (6 g) in water (100 cm3). The aqueous phase was extracted further with chloroform (3×50 cm3) and the combined and dried (MgSO4) extracts were concentrated in vacuo to give an oil. This oil was chromatographed on silica (Merck "MK 60.9385") eluting with ethyl acetate. The fractions containing the product were combined and evaporated to afford a solid which was recrystallised from hexane to afford 2-methoxy-8-methyl-6-(3-pyridyl)quinoline, m.p. 117°-118.5°, (1.12 g).

Workup

  1. temperaturethe resulting solution was warmed to 0°
  2. additionwas then added
  3. temperaturethe mixture was heated
  4. temperatureunder reflux for 2 hours
  5. temperatureThe reaction mixture was cooled
  6. concentrationconcentrated in vacuo
  7. additiontreated with chloroform (100 cm3)
  8. extractionThe aqueous phase was extracted further with chloroform (3×50 cm3)
  9. dry with materialdried (MgSO4) extracts
  10. concentrationwere concentrated in vacuo
  11. customto give an oil
  12. customThis oil was chromatographed on silica (Merck "MK 60.9385")
  13. washeluting with ethyl acetate
  14. additionThe fractions containing the product
  15. customevaporated
  16. customto afford a solid which
  17. customwas recrystallised from hexane

Sources & evidence

ORD record
ord-b86c1f299d2047a7982d3e35bc326eb1
Source dataset
uspto-grants-1987_12
Patent number
US04710507

Reaction notes

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