4-Bromoanisole → 2-Methoxy-6-(4-methoxyphenyl)-8-methylquinoline

HRID 568351Notes

Reaction equation

HRID 568351 reaction equation
C([Li])CCC.Br[C:7]1[CH:12]=[CH:11][C:10]([O:13][CH3:14])=[CH:9][CH:8]=1.Br[C:16]1[CH:17]=[C:18]2[C:23](=[C:24]([CH3:26])[CH:25]=1)[N:22]=[C:21]([O:27][CH3:28])[CH:20]=[CH:19]2>CCCCCC.C1COCC1.[Cl-].[Zn+2].[Cl-].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:28][O:27][C:21]1[CH:20]=[CH:19][C:18]2[C:23](=[C:24]([CH3:26])[CH:25]=[C:16]([C:7]3[CH:12]=[CH:11][C:10]([O:13][CH3:14])=[CH:9][CH:8]=3)[CH:17]=2)[N:22]=1

Participants

8

Reactant 3

HCID 77304-BromoanisoleHCID 14220967HCID 14220967, compoundHCID 178418339Butyllithium

Product 1

HCID 201504532-Methoxy-6-(4-methoxyphenyl)-8-methylquinoline

Reagents, catalysts & solvents 4

HCID 3007855ZincchlorideCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Procedure

n-Butyllithium (33.3 cm3 of a 1.5M solution in n-hexane) was added dropwise at -70° to a stirred solution of 4-bromoanisole (6.26 cm3) in THF (70 cm3) under nitrogen. After ten minutes, a solution of anhydrous zinc chloride (6.814 g) in THF (50 cm3) was added and the mixture was allowed to warm to room temperature over 0.5 hour. A mixture of 6-bromo-2-methoxy-8-methylquinoline (12.8 g) and tetrakis(triphenylphosphine)palladium (0) (0.5 g) was added and the mixture heated under reflux for 2 hours. Volatile material was removed in vacuo and the residue was partitioned between chloroform (150 cm3) and a solution of ethylenediaminetetraacetic acid (40 g) in water (250 cm3). The organic layer was dried (MgSO4) and evaporated to afford an oil which was chromatographed on silica (Merck "MK 60.9385" [Trade Mark]) eluting with hexane:ethyl acetate, 19:1. Combination and evaporation of the appropriate fractions afforded the title compound (5.49 g). A small portion of this was recrystallised from methanol and had m.p. of 104°-106° and the following analysis:

Workup

  1. waitAfter ten minutes
  2. additionwas added
  3. temperaturethe mixture heated
  4. temperatureunder reflux for 2 hours
  5. customVolatile material was removed in vacuo
  6. customthe residue was partitioned between chloroform (150 cm3)
  7. dry with materialThe organic layer was dried (MgSO4)
  8. customevaporated
  9. customto afford an oil which
  10. customwas chromatographed on silica (Merck "MK 60.9385" [Trade Mark])
  11. washeluting with hexane
  12. customCombination and evaporation of the appropriate fractions

Sources & evidence

ORD record
ord-32b1d0fb7a894ede8724d19645242259
Source dataset
uspto-grants-1988_03
Patent number
US04728654

Reaction notes

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