Malonic Acid → 2,4-Dichloro-6-methoxy-8-methyl-quinoline

HRID 880765Notes

Reaction equation

HRID 880765 reaction equation
[CH3:1][O:2][C:3]1[CH:9]=[CH:8][C:6]([NH2:7])=[C:5]([CH3:10])[CH:4]=1.[C:11](O)(=O)[CH2:12][C:13](O)=O.O.[Cl-:19].[Cl-:20].[Cl-].[P+3]=O>>[Cl:19][C:13]1[CH:12]=[C:11]([Cl:20])[C:8]2[C:6](=[C:5]([CH3:10])[CH:4]=[C:3]([O:2][CH3:1])[CH:9]=2)[N:7]=1

Participants

5

Reactant 4

HCID 867Malonic AcidHCID 962WaterHCID 76102-Methyl-4-methoxyanilineHCID 178527001HCID 178527001, compound

Product 1

HCID 866277502,4-Dichloro-6-methoxy-8-methyl-quinolineYield 43%

Procedure

A mixture of 4-methoxy-2-methyl aniline 215f (5 g, 36.45 mmol), malonic acid (5.68 g, 54.67 mmol) in phosphorus oxide trichloride (36 mL) was refluxed for 16 hrs. The reaction mixture was then poured dropwise into cooled water (400 mL), extracted with ethyl acetate, washed with brine, dried over Na2SO4, filtered, concentrated under reduced pressure, and purified by chromatography on silica gel (DCM) to yield compound 220f as a beige solid in 43% yield. 1H NMR (CDCl3, 400 MHz) δ (ppm) 2.72 (s, 3H), 3.95 (s, 3H), 7.27-7.28 (m, 2H), 7.47 (s, 1H).

Workup

  1. temperaturewas refluxed for 16 hrs
  2. additionThe reaction mixture was then poured dropwise
  3. extractionextracted with ethyl acetate
  4. washwashed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. custompurified by chromatography on silica gel (DCM)

Sources & evidence

ORD record
ord-2c2600b95772478f89bd58e4ade85d5e
Source dataset
uspto-grants-2015_03
Patent number
US08993595B2

Reaction notes

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