Acetic Acid → Ethyl 5,7-dichloro-8-methoxyquinoline-3-carboxylate

HRID 872241Notes

Reaction equation

HRID 872241 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[CH:7]=[N:8][C:9]2[C:14]([C:15]=1Cl)=[C:13]([Cl:17])[CH:12]=[C:11]([Cl:18])[C:10]=2[O:19][CH3:20])=[O:5])[CH3:2].C(O)(=O)C.C(OCC)(=O)C>O1CCOCC1.[Zn]>[CH2:1]([O:3][C:4]([C:6]1[CH:7]=[N:8][C:9]2[C:14]([CH:15]=1)=[C:13]([Cl:17])[CH:12]=[C:11]([Cl:18])[C:10]=2[O:19][CH3:20])=[O:5])[CH3:2]

Participants

6

Reactant 3

HCID 176Acetic AcidHCID 8857Ethyl AcetateHCID 57939336Ethyl 4,5,7-trichloro-8-methoxyquinoline-3-carboxylate

Product 1

HCID 57939343Ethyl 5,7-dichloro-8-methoxyquinoline-3-carboxylateYield 39.7%

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 312751,4-DioxaneSolvent

Procedure

A suspension of zinc powder (0.70 g) was stirred at 20° C. in a solution of 4,5,7-trichloro-8-methoxy-quinoline-3-carboxylic acid ethyl ester 26 (364 mg, 1.09 mmol) and acetic acid (2.2 ml) in 1,4-dioxane (15 ml). After 20 minutes, ethyl acetate (20 ml) was added and the resultant mixture filtered through a pad of celite. The filtrate was washed with saturated aqueous sodium chloride solution (10 ml), dried (MgSO4), filtered, and the solvent removed under vacuum. The residue was chromatographed on flash silica (ethyl acetate/hexane, 1:9), yielding 130 mg (39%) of the title compound 27 as a white solid. 1H NMR (CDCl3, 400 MHz): δ 9.51 (d, J=2.0, 1 H), 9.15 (d, J=2.0, 1 H), 7.72 (s, 1 H), 4.51 (q, J=7.2, 2 H), 4.18 (s, 3 H), 1.47 (t, J=7.2, 3 H).

Workup

  1. filtrationthe resultant mixture filtered through a pad of celite
  2. washThe filtrate was washed with saturated aqueous sodium chloride solution (10 ml)
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. customthe solvent removed under vacuum
  6. customThe residue was chromatographed on flash silica (ethyl acetate/hexane, 1:9)

Sources & evidence

ORD record
ord-59eea77a77e44de7969cf6827d6f3d4d
Source dataset
uspto-grants-2015_03
Patent number
US08975278B2

Reaction notes

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