Sulfuric Acid → 3-Benzyloxy-5-hydroxypyridine

HRID 2305714Notes

Reaction equation

HRID 2305714 reaction equation
[C:1]1([CH2:7][O:8][C:9]2[CH:10]=[C:11](N)[CH:12]=[N:13][CH:14]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.S(=O)(=O)(O)[OH:17].N([O-])=O.[Na+].[OH-].[Na+].[Na+].[Cl-]>O>[C:1]1([CH2:7][O:8][C:9]2[CH:10]=[C:11]([OH:17])[CH:12]=[N:13][CH:14]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

7

Reactant 5

HCID 1118Sulfuric Acid2×HCID 5234Sodium ChlorideHCID 14798Sodium HydroxideHCID 229897355-(Benzyloxy)pyridin-3-amineHCID 23668193Sodium Nitrite

Product 1

HCID 229897043-Benzyloxy-5-hydroxypyridine

Reagents, catalysts & solvents 1

HCID 962WaterSolvent3×

Procedure

The 5-(phenylmethoxy)-3-pyridylamine (1.61 g, 8.00 mmol) was stirred into concentrated sulfuric acid (1.7 mL), water (2.5 mL) and ice (4 g). This mixture was allowed to stir for 10 min until the solution became homogeneous. To this cold, stirring solution was added a solution of sodium nitrite (552 mg, 8.00 mmol) in water (2 mL). The mixture was allowed to stir for 10 min. A boiling solution of concentrated sulfuric acid (5 mL) and water (4 mL) was added. The mixture was heated until all solids dissolved. Ice was added to cool the reaction. The pH was adjusted to 8 with 10% NaOH solution and saturated NaCl solution was added. The product was extracted with ethyl acetate (4×100 mL). The combined ethyl acetate extracts were dried (Na2SO4), filtered, concentrated by rotary evaporation and briefly vacuum to give 1.52 g (94.4%).

Workup

  1. stirringTo this cold, stirring solution
  2. stirringto stir for 10 min
  3. temperatureThe mixture was heated until all solids
  4. dissolutiondissolved
  5. additionIce was added
  6. temperatureto cool
  7. customthe reaction
  8. additionwas added
  9. extractionThe product was extracted with ethyl acetate (4×100 mL)
  10. dry with materialThe combined ethyl acetate extracts were dried (Na2SO4)
  11. filtrationfiltered
  12. concentrationconcentrated by rotary evaporation and briefly vacuum
  13. customto give 1.52 g (94.4%)

Sources & evidence

ORD record
ord-cc8d744e91514fb79c5e9d8619725ce3
Source dataset
uspto-grants-2002_08
Patent number
US06441006B2

Reaction notes

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