Malonic Acid → 3-(3-Chloro-2,4-dimethoxyphenyl)prop-2-enoic acid

HRID 488545Notes

Reaction equation

HRID 488545 reaction equation
[Cl:1][C:2]1[C:3]([O:12][CH3:13])=[C:4]([CH:7]=[CH:8][C:9]=1[O:10][CH3:11])[CH:5]=O.C(O)(=O)[CH2:15][C:16]([OH:18])=[O:17].N1CCCCC1>N1C=CC=CC=1>[Cl:1][C:2]1[C:3]([O:12][CH3:13])=[C:4]([CH:5]=[CH:15][C:16]([OH:18])=[O:17])[CH:7]=[CH:8][C:9]=1[O:10][CH3:11]

Participants

5

Reactant 3

HCID 867Malonic AcidHCID 8082PiperidineHCID 133437053-Chloro-2,4-dimethoxybenzaldehyde

Product 1

HCID 688767863-(3-Chloro-2,4-dimethoxyphenyl)prop-2-enoic acidYield 95%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

A solution of compound (2a) (11.07 g, 55.2 mmol), malonic acid (8.639 g, 83 mmol) and piperidine (2 ml, 1.722 g, 20.2 mmol) in 80 ml of anhydrous pyridine was refluxed (bath temperature 110° C.) for 2 h. Reaction mixture was cooled, concentrated under vacuum and acidified 250 ml of 5% aqueous citric acid to a pH of 3. Resulted heterogeneous mixture was sonicated for a few minutes. The precipitated material was filtered off, washed with water (2×20 ml) and dried in vacuum over KOH to give 12.7 g (52.3 mmol, 95% yield) of pure (HPLC, 1H NMR) desired acid 3a as a white solid. 1H NMR (DMSO-d6): δ 7.77 (d, J=9.0 Hz, 1H), 7.67 (d, J=16.0 Hz, 1H), 7.01 (d, J=9.0 Hz, 1H), 6.51 (d, J=16.0 Hz, 1H), 3.90 (s, 3H), 3.77 (s, 3H).

Workup

  1. customReaction mixture
  2. temperaturewas cooled
  3. concentrationconcentrated under vacuum
  4. customResulted heterogeneous mixture
  5. customwas sonicated for a few minutes
  6. filtrationThe precipitated material was filtered off
  7. washwashed with water (2×20 ml)
  8. dry with materialdried in vacuum over KOH

Sources & evidence

ORD record
ord-3f9e75f601d24736b5764f03b2d30c0e
Source dataset
uspto-grants-2005_12
Patent number
US06972339B2

Reaction notes

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