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

HRID 530726Notes

Reaction equation

HRID 530726 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-023531de395c46e9b17357fb371afea8
Source dataset
uspto-grants-2016_05
Patent number
US09353100B2

Reaction notes

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