Acetic Acid → Methyl (4-amino-2-fluoro-3-hydroxyphenyl)acetate

HRID 1372573Notes

Reaction equation

HRID 1372573 reaction equation
[F:1][C:2]1[C:7]([OH:8])=[C:6]([N+:9]([O-])=O)[CH:5]=[CH:4][C:3]=1[CH2:12][C:13]([O:15][CH3:16])=[O:14].O.O.O.C([O-])(=O)C.[Na+].C(O)(=O)C>CO.O>[NH2:9][C:6]1[CH:5]=[CH:4][C:3]([CH2:12][C:13]([O:15][CH3:16])=[O:14])=[C:2]([F:1])[C:7]=1[OH:8]

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 23665404Sodium Acetate TrihydrateHCID 58778448Methyl 2-fluoro-3-hydroxy-4-nitrophenylacetate

Product 1

HCID 17859032Methyl (4-amino-2-fluoro-3-hydroxyphenyl)acetateYield 44%

Reagents, catalysts & solvents 1

HCID 22242641Methanol--water (1/1)Solvent

Procedure

Methyl 2-fluoro-3-hydroxy-4-nitrophenylacetate (5.22 g, 14.9 mmol), reduced iron powder (2.66 g, 47.7 mmol), sodium acetate-trihydrate (2.03 g, 14.9 mmol) and acetic acid (5.54 ml) were heated and refluxed at 110° C. for 4 hours in methanol:water (1:4, 300 ml). After cooling to room temperature, the reaction mixture was filtered through Celite under reduced pressure to remove the insoluble matter. The filtrate was then concentrated, followed by extraction with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous sodium sulfate and distilled under reduced pressure to remove the solvent. The residue was purified by chromatography on a silica gel column (silica gel: 50 g), whereby from hexane/ethyl acetate (2/1) eluate fractions, the title compound (1.29 g, 44%) was obtained as a brown oil.

Workup

  1. filtrationthe reaction mixture was filtered through Celite under reduced pressure
  2. customto remove the insoluble matter
  3. concentrationThe filtrate was then concentrated
  4. extractionfollowed by extraction with ethyl acetate
  5. washThe extract was washed with saturated brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. distillationdistilled under reduced pressure
  8. customto remove the solvent
  9. customThe residue was purified by chromatography on a silica gel column (silica gel: 50 g), whereby from hexane/ethyl acetate (2/1) eluate fractions

Sources & evidence

ORD record
ord-a4499fd98714466786c41073f0f216b1
Source dataset
uspto-grants-2007_01
Patent number
US07157487B2

Reaction notes

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