Citric Acid → 2-(4-(4-Amino-2-nitrophenoxy)-2,3-dimethylphenyl)acetic acid

HRID 2423287Notes

Reaction equation

HRID 2423287 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([OH:11])=[O:10])=[C:4]([CH3:12])[C:3]=1[CH3:13].C(=O)([O-])[O-].[Cs+].[Cs+].F[C:21]1[CH:27]=[CH:26][C:24]([NH2:25])=[CH:23][C:22]=1[N+:28]([O-:30])=[O:29].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>CS(C)=O.O>[NH2:25][C:24]1[CH:26]=[CH:27][C:21]([O:1][C:2]2[CH:7]=[CH:6][C:5]([CH2:8][C:9]([OH:11])=[O:10])=[C:4]([CH3:12])[C:3]=2[CH3:13])=[C:22]([N+:28]([O-:30])=[O:29])[CH:23]=1

Participants

7

Reactant 4

HCID 311Citric AcidHCID 10796Cesium carbonateHCID 677684-Fluoro-3-nitroanilineHCID 598647702-(4-Hydroxy-2,3-dimethylphenyl)acetic acid

Product 1

HCID 598648252-(4-(4-Amino-2-nitrophenoxy)-2,3-dimethylphenyl)acetic acid

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Procedure

Under an N2 atmosphere, 2-(4-hydroxy-2,3-dimethylphenyl)acetic acid (0.780 g, 4.33 mmol) was dissolved in DMSO (29 mL). Cesium carbonate (3.53 g, 10.8 mmol) was added and the reaction was allowed to stir at room temperature for 5 min. 4-Fluoro-3-nitroaniline (0.678 g, 4.33 mmol) was added and the reaction was heated to 80° C. for 2.25 h. The reaction was allowed to cool to room temperature and diluted with water. Citric acid was added to pH 4 and the reaction was extracted with ethyl acetate. The layers were separated and the aqueous layer was washed with additional ethyl acetate. The organics were combined, dried (Na2SO4), filtered, and concentrated in vacuo. Flash column chromatography of the residue, eluting with 0% to 8% methanol in dichloromethane, afforded the title compound. LC-MS ESI (pos.) m/z: 317.2 (M+H).

Workup

  1. temperaturethe reaction was heated to 80° C. for 2.25 h
  2. temperatureto cool to room temperature
  3. extractionthe reaction was extracted with ethyl acetate
  4. customThe layers were separated
  5. washthe aqueous layer was washed with additional ethyl acetate
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. washFlash column chromatography of the residue, eluting with 0% to 8% methanol in dichloromethane

Sources & evidence

ORD record
ord-f366ac2c3cef43c8884261cff646ce87
Source dataset
uspto-grants-2011_06
Patent number
US07960567B2

Reaction notes

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