Benzyl Bromide → 1,6-Naphthyridine, 5,6,7,8-tetrahydro-6-(phenylmethyl)-

HRID 2247945Notes

Reaction equation

HRID 2247945 reaction equation
[N:1]1[C:10]2[C:5](=[CH:6][N:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1.[CH2:11](Br)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.[BH4-].[Na+]>C(#N)C>[CH2:11]([N:7]1[CH2:8][CH2:9][C:10]2[N:1]=[CH:2][CH:3]=[CH:4][C:5]=2[CH2:6]1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1

Participants

5

Reactant 3

HCID 7498Benzyl BromideHCID 674881,6-Naphthyridine2×HCID 4311764Sodium borohydride

Product 1

HCID 30587131,6-Naphthyridine, 5,6,7,8-tetrahydro-6-(phenylmethyl)-Yield 51.4%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

1,6-Naphthyridine (13.7 g, 105 mmol) and benzyl bromide (36.05 g, 210 mmol) were combined in acetonitrile (200 ml) and heated to reflux until no 1,6-naphthyridine was visible by thin layer chromatography. After removal of the solvent in vacuo, the residue was washed several times with ether and dissolved in methanol (700 ml). Water (250 ml) was added, and the solution cooled to 0°; portionwise addition of sodium borohydride (20.8 g, 550 mmol) brought about vigorous gas evolution and a slight rise in temperature. The reaction mixture was allowed to warm to room temperature and stir for 18 hours. The solvent was then removed in vacuo and the residue partitioned between water (750 ml) and methylene chloride (300 ml). The aqueous layer was extracted with additional methylene chloride (2×300 ml) and the combined organic extracts were washed once with water and once with saturated aqueous sodium chloride. Removal of solvent provided a dark amber foam, which was purified by column chromatography (99:1 methylene chloride:methanol) to yield the title product (12.1 g, 54 mmol, 51% yield).

Workup

  1. temperatureheated
  2. customAfter removal of the solvent in vacuo
  3. washthe residue was washed several times with ether
  4. dissolutiondissolved in methanol (700 ml)
  5. additionWater (250 ml) was added
  6. temperaturethe solution cooled to 0°
  7. customThe solvent was then removed in vacuo
  8. customthe residue partitioned between water (750 ml) and methylene chloride (300 ml)
  9. extractionThe aqueous layer was extracted with additional methylene chloride (2×300 ml)
  10. washthe combined organic extracts were washed once with water and once with saturated aqueous sodium chloride
  11. customRemoval of solvent
  12. customprovided a dark amber foam, which
  13. customwas purified by column chromatography (99:1 methylene chloride:methanol)

Sources & evidence

ORD record
ord-0de9121bcd0742bd91ee751f75e1cecf
Source dataset
uspto-grants-1991_08
Patent number
US05037834

Reaction notes

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