Citric Acid → 5-Chloro-2-[(4-chlorophenoxy)methyl]-3-pyridinecarboxylic acid

HRID 660233Notes

Reaction equation

HRID 660233 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:10](=[O:11])[O:9][CH2:8][C:5]2=[N:6][CH:7]=1.[Cl:12][C:13]1[CH:18]=[CH:17][C:16]([OH:19])=[CH:15][CH:14]=1.C[O-].[Na+].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>>[Cl:1][C:2]1[CH:7]=[N:6][C:5]([CH2:8][O:19][C:16]2[CH:17]=[CH:18][C:13]([Cl:12])=[CH:14][CH:15]=2)=[C:4]([CH:3]=1)[C:10]([OH:9])=[O:11]

Participants

5

Reactant 4

HCID 311Citric AcidHCID 46844-ChlorophenolHCID 10942334Sodium MethoxideHCID 54776268HCID 54776268, compound

Product 1

HCID 688622195-Chloro-2-[(4-chlorophenoxy)methyl]-3-pyridinecarboxylic acidYield 58.3%

Conditions

Temperature
130 °C

Procedure

A mixture of 3-chlorofuro[3,4-b]pyridin-5(7H)-one (step 1, 110 mg, 0.65 mmol) and 4-chloro phenol (416 mg, 3.24 mmol) was heated to 130° C. under N2, then sodium methoxide (28% methanol solution, 250 mg, 1.30 mmol) was added dropwise to the mixture at 130° C. The mixture was heated at the same temperature for 4 hours. After cooling, to the mixture was added 10% aqueous citric acid and the mixture was extracted with ethyl acetate. The extracts were dried over sodium sulfate and evaporated. The residue was purified by flash column chromatography on silica gel to afford 113 mg of the title compound:

Workup

  1. temperatureThe mixture was heated at the same temperature for 4 hours
  2. temperatureAfter cooling, to the mixture
  3. extractionthe mixture was extracted with ethyl acetate
  4. dry with materialThe extracts were dried over sodium sulfate
  5. customevaporated
  6. customThe residue was purified by flash column chromatography on silica gel

Sources & evidence

ORD record
ord-d7323d1ad50c48cc8158b3ab4a126020
Source dataset
uspto-grants-2011_12
Patent number
US08084476B2

Reaction notes

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