Acetic Acid → Ethyl 8-bromoquinoline-3-carboxylate

HRID 1005670Notes

Reaction equation

HRID 1005670 reaction equation
[C:1]([C:6]1[CH:7]=[N:8][C:9]2[C:14]([C:15]=1O)=[CH:13][CH:12]=[CH:11][C:10]=2[Br:17])([O:3][CH2:4][CH3:5])=[O:2].P(Cl)(Cl)(Cl)=O.C(O)(=O)C.C(OCC)(=O)C>O1CCOCC1.[Zn]>[C:1]([C:6]1[CH:7]=[N:8][C:9]2[C:14]([CH:15]=1)=[CH:13][CH:12]=[CH:11][C:10]=2[Br:17])([O:3][CH2:4][CH3:5])=[O:2]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 8857Ethyl AcetateHCID 24813Phosphorus oxychloride2×HCID 178469454Ethyl 8-bromo-4-oxo-1,4-dihydroquinoline-3-carboxylate

Product 1

HCID 22674138Ethyl 8-bromoquinoline-3-carboxylateYield 7.6%

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
65 °C

Procedure

A mixture of 2.5 g (8.4 mmol) of 3-carbethoxy-4-hydroxy-8-bromoquinoline and 10 ml of phosphorus oxychloride was heated under reflux for 1 hour. After the completion of the reaction, phosphorus oxychloride was removed and the residue was purified by NH silica gel, to give 2.6 g of a chlorinated derivative. Next, 500 mg (1.6 mmol) of the chlorinated derivative was dissolved in 20 ml of dioxane, and 1 g of powdered zinc and 3 ml of acetic acid were added thereto, followed by heating at 65° C. for 30 minutes. To the reaction mixture was added ethyl acetate, followed by filtering through Celite. The filtrate was washed with brine, dried over magnesium sulfate and concentrated. To the residue was added 1 ml of acetic acid, and the mixture was left stand for 12 hours. Then, acetic acid was removed, and the residue was subjected to silica gel column chromatography and eluted with an eluent (ethyl acetate-n-hexane=1-7), to give 180 mg of the title compound.

Workup

  1. temperaturewas heated
  2. temperatureunder reflux for 1 hour
  3. customwas removed
  4. customthe residue was purified by NH silica gel
  5. customto give 2.6 g of a chlorinated derivative
  6. filtrationby filtering through Celite
  7. washThe filtrate was washed with brine
  8. dry with materialdried over magnesium sulfate
  9. concentrationconcentrated
  10. additionTo the residue was added 1 ml of acetic acid
  11. customThen, acetic acid was removed
  12. washeluted with an eluent (ethyl acetate-n-hexane=1-7)

Sources & evidence

ORD record
ord-0629495639844b2cb4e5f8be5827e8b1
Source dataset
uspto-grants-2004_09
Patent number
US06787534B2

Reaction notes

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