Phenol → 5-Chloro-3-phenoxy-2-pyridinamine

HRID 1370594Notes

Reaction equation

HRID 1370594 reaction equation
Br[C:2]1[C:3]([NH2:9])=[N:4][CH:5]=[C:6]([Cl:8])[CH:7]=1.[C:10]1([OH:16])[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.[OH-].[K+].C(COC)OC>S([O-])([O-])(=O)=O.[Cu+2].O>[Cl:8][C:6]1[CH:7]=[C:2]([O:16][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[C:3]([NH2:9])=[N:4][CH:5]=1

Participants

7

Reactant 4

HCID 996PhenolHCID 80711,2-DimethoxyethaneHCID 14797Potassium HydroxideHCID 27639713-Bromo-5-chloropyridin-2-amine

Product 1

HCID 187528795-Chloro-3-phenoxy-2-pyridinamineYield 24%

Reagents, catalysts & solvents 2

HCID 24462Copper SulfateCatalystHCID 962WaterSolvent

Procedure

3-Bromo-5-chloro-2-pyridinamine (520 mg, 2.5 mmol), phenol (2.0 g, 21.3 mmol), potassium hydroxide (flakes, 85%, 600 mg, 9.1 mmol) and anhydrous copper (II) sulphate (100 mg, 0.6 mmol) and dimethoxyethane (250 μl) were heated together at 140° C. for 2 h, allowed to cool and the mixture poured into water (50 ml). EtOAc extracts (5×15 ml) were filtered through celite and extracted into 2N HCl (4×10 ml). The combined aqueous extracts were basified with NaOH and re-extracted into EtOAc (3×20 ml), dried over MgSO4, and concentrated to a brown oil (230 mg). Purification by column chromatography on silica gel eluting with hexane—EtOAc (80:20) gave the title compound as a white solid (136 mg, 0.6 mmol). An analytical sample was prepared by crystallisation from hexane:

Workup

  1. temperatureto cool
  2. filtrationEtOAc extracts (5×15 ml) were filtered through celite
  3. extractionextracted into 2N HCl (4×10 ml)
  4. extractionre-extracted into EtOAc (3×20 ml)
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated to a brown oil (230 mg)
  7. customPurification by column chromatography on silica gel eluting with hexane—EtOAc (80:20)

Sources & evidence

ORD record
ord-3663db6db9bc428c9a6fd268f1a9ebe3
Source dataset
uspto-grants-2003_06
Patent number
US06583162B1

Reaction notes

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