5-Benzyloxy-2-fluoro-4-methylaniline → 5-Benzyloxy-2-fluoro-4-methylphenol

HRID 1057348Notes

Reaction equation

HRID 1057348 reaction equation
N([O-])=[O:2].[Na+].[CH2:5]([O:12][C:13]1[C:14]([CH3:21])=[CH:15][C:16]([F:20])=[C:17]([CH:19]=1)N)[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1>O.C(O)(=O)C.S(=O)(=O)(O)O.O.O.O.[N+]([O-])([O-])=O.[Cu+2].[N+]([O-])([O-])=O.[Cu]=O>[CH2:5]([O:12][C:13]1[C:14]([CH3:21])=[CH:15][C:16]([F:20])=[C:17]([OH:2])[CH:19]=1)[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1

Participants

8

Reactant 2

HCID 219910685-Benzyloxy-2-fluoro-4-methylanilineHCID 23668193Sodium Nitrite

Product 1

HCID 219910495-Benzyloxy-2-fluoro-4-methylphenolYield 27%

Reagents, catalysts & solvents 5

HCID 14829Copper oxideCatalystHCID 9837674Copper(II) nitrate trihydrateCatalystHCID 176Acetic AcidSolventHCID 962WaterSolvent2×HCID 1118Sulfuric AcidSolvent

Procedure

The starting material 5-benzyloxy-2-fluoro-4-methylphenol, was obtained by adding a solution of sodium nitrite (1.68 g, 24 mmol) in water (3.5 ml), dropwise, to a solution of 5-benzyloxy-2-fluoro-4-methylaniline (4.7 g, 20 mmol) in acetic acid (82 ml) and 70% sulphuric acid (3.15 ml) cooled at 10° C. The mixture was stirred vigorously for 20 minutes, then a solution of copper(II)nitrate trihydrate (481 g, 2 mol) in water (790 ml) was added, followed by copper(II)oxide (3 g, 19 mmol). After stirring for 3 hours, the mixture was extracted with ethyl acetate. The organic layer was washed with water and then brine, dried (MgSO4) and the solvent evaporated. The resulting oil was purified by flash chromatography using petroleum ether/ether (85/15) as eluent to give 5-benzyloxy-2-fluoro-4-methylphenol as an orange oil (1.25 g, 27%).

Workup

  1. stirringAfter stirring for 3 hours
  2. extractionthe mixture was extracted with ethyl acetate
  3. washThe organic layer was washed with water
  4. dry with materialbrine, dried (MgSO4)
  5. customthe solvent evaporated
  6. customThe resulting oil was purified by flash chromatography

Sources & evidence

ORD record
ord-5f4d5c760cd54487b1a924c580c6727a
Source dataset
uspto-grants-2003_02
Patent number
US06514971B1

Reaction notes

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