Malonic Acid → 2,4,8-Trichloro-7-methoxyquinoline

HRID 530724Notes

Reaction equation

HRID 530724 reaction equation
[ClH:1].[Cl:2][C:3]1[C:9]([O:10][CH3:11])=[CH:8][CH:7]=[CH:6][C:4]=1[NH2:5].[C:12](O)(=O)[CH2:13][C:14](O)=O.O(Cl)[Cl:20].[P]>O>[Cl:1][C:14]1[CH:13]=[C:12]([Cl:20])[C:6]2[C:4](=[C:3]([Cl:2])[C:9]([O:10][CH3:11])=[CH:8][CH:7]=2)[N:5]=1

Participants

5

Reactant 3

HCID 867Malonic AcidHCID 248201302-Chloro-3-methoxyaniline hydrochlorideHCID 178479709HCID 178479709, compound

Product 1

HCID 27945162,4,8-Trichloro-7-methoxyquinolineYield 74%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A mixture of 2-chloro-3-methoxyaniline hydrochloride 215d (15 g, 1 eq.), malonic acid (12.06 g, 1.5 eq.), and phosphorus oxochloride (80 mL) was refluxed for 16 hrs. The reaction mixture was slowly poured into water and extracted with DCM. The organic layer was dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude material was purified on silica pad, eluted with DCM, to yield compound 220d as a white solid in 74% yield. 1H NMR (CDCl3, 376 MHz) δ 4.10 (s, 3H), 7.43 (t, J=4.88 Hz, 2H), 8.12 (d, J=9.48 Hz, 1H).

Workup

  1. temperaturewas refluxed for 16 hrs
  2. extractionextracted with DCM
  3. dry with materialThe organic layer was dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe crude material was purified on silica pad
  7. washeluted with DCM

Sources & evidence

ORD record
ord-35aff3fb39fa404e9872d6cead9f8f2f
Source dataset
uspto-grants-2016_05
Patent number
US09353100B2

Reaction notes

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