1-(2-Bromoethyl)-4-methoxybenzene → 6-Benzyl-5-[2-(4-methoxy-phenyl)-ethyl]-5,6-dihydro-[1,6]naphthyridine

HRID 563926Notes

Reaction equation

HRID 563926 reaction equation
[Mg].[CH3:2][O:3][C:4]1[CH:12]=[CH:11][C:7]([CH2:8][CH2:9]Br)=[CH:6][CH:5]=1.[Br-].[CH2:14]([N+:21]1[CH:22]=[C:23]2[C:28](=[CH:29][CH:30]=1)[N:27]=[CH:26][CH:25]=[CH:24]2)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1>C1COCC1>[CH2:14]([N:21]1[CH:30]=[CH:29][C:28]2[N:27]=[CH:26][CH:25]=[CH:24][C:23]=2[CH:22]1[CH2:9][CH2:8][C:7]1[CH:11]=[CH:12][C:4]([O:3][CH3:2])=[CH:5][CH:6]=1)[C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1

Participants

5

Reactant 3

HCID 844271-(2-Bromoethyl)-4-methoxybenzeneHCID 5462224MagnesiumHCID 131938656-Benzyl-[1,6]naphthyridin-6-ium bromide

Product 1

HCID 598200166-Benzyl-5-[2-(4-methoxy-phenyl)-ethyl]-5,6-dihydro-[1,6]naphthyridineYield 90.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a suspension of 581 mg (23.9 mmol) magnesium in 24 mL THF was added 5.3 g (23.9 mmol) 4-methoxyphenethyl bromide. The mixture was refluxed for 2 h and then cooled in an ice bath and 2.4 g (7.97 mmol) 6-benzyl-[1,6]naphthyridin-6-ium bromide (Chemical & Pharmaceutical Bulletin, 32(7), 2522-9; 1984) was added at once. The mixture was stirred at room temperature for 30 minutes, cooled to 0° C. and quenched with a 20% NH4Cl solution. The mixture was extracted with ethyl acetate. The combined extracts were dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified on silica eluting with a gradient formed from heptane and ethyl acetate. The product containing fractions were evaporated to yield 2.57 g (90%) of the title compound was yielded as yellow oil.

Workup

  1. temperatureThe mixture was refluxed for 2 h
  2. temperaturecooled in an ice bath
  3. temperaturecooled to 0° C.
  4. customquenched with a 20% NH4Cl solution
  5. extractionThe mixture was extracted with ethyl acetate
  6. dry with materialThe combined extracts were dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified on silica eluting with a gradient
  10. customformed from heptane and ethyl acetate
  11. additionThe product containing fractions
  12. customwere evaporated

Sources & evidence

ORD record
ord-4123bac4c84946489b5a172306d15c3d
Source dataset
uspto-grants-2011_11
Patent number
US08067598B2

Reaction notes

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