Nitric Acid → 3-Fluoro-4-methoxyaniline

HRID 1388564Notes

Reaction equation

HRID 1388564 reaction equation
C([NH:4][C:5]1[CH:10]=[CH:9][C:8]([O:11][CH3:12])=[C:7]([F:13])[CH:6]=1)(=O)C.[N+]([O-])(O)=O>C(O)(=O)C.C(OC(=O)C)(=O)C>[NH2:4][C:5]1[CH:10]=[CH:9][C:8]([O:11][CH3:12])=[C:7]([F:13])[CH:6]=1

Participants

5

Reactant 2

HCID 944Nitric AcidHCID 10397459HCID 10397459, compound

Product 1

HCID 5811103-Fluoro-4-methoxyanilineYield 1,114.4%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 7918Acetic AnhydrideSolvent

Procedure

To a cold (15°), stirred solution of 12.8 g (0.0699 mol) of 4-acetamido-2-fluoroanisole in 55 mL of acetic acid and 27 mL of acetic anhydride was added, dropwise, 6.5 g (0.072 mol) of 70% nitric acid (sp. gr. 1.424) at such a rate that the temperature of the reaction mixture did not exceed 16°. The solution was stirred for 1.5 hours at room temperature then poured into 400 mL of ice-water. The aqueous suspension was extracted with methylene chloride (1×300 mL; 1×200 mL), then the combined extracts were concentrated in vacuo to a solid (13 g). The material was chromatographed on a column of silica gel (300 g) using benzene as the eluent. The fractions containing the required product were combined then concentrated in vacuo. The solid residue was dissolved in methylene chloride (400 mL) and the solution was washed with water, dried over anhydrous magnesium sulfate, then concentrated in vacuo; yield, 10.0 g (62.9%). The material was suitable for further transformation. Additional material (169 g; 44.6%) was obtained from 110 g (0.779 mol) of 4-amino-2-fluoroanisole without isolating the intermediate 4-acetamido-2-fluoroanisole (3).

Workup

  1. additionwas added
  2. customdid not exceed 16°
  3. extractionThe aqueous suspension was extracted with methylene chloride (1×300 mL; 1×200 mL)
  4. concentrationthe combined extracts were concentrated in vacuo to a solid (13 g)
  5. customThe material was chromatographed on a column of silica gel (300 g)
  6. additionThe fractions containing the required product
  7. concentrationwere combined then concentrated in vacuo
  8. dissolutionThe solid residue was dissolved in methylene chloride (400 mL)
  9. washthe solution was washed with water
  10. dry with materialdried over anhydrous magnesium sulfate
  11. concentrationconcentrated in vacuo
  12. customyield

Sources & evidence

ORD record
ord-2687f0f8df7d493e83b2e0dd54bbc8b5
Source dataset
uspto-grants-1984_02
Patent number
US04431807

Reaction notes

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