3-Nitrophenol → 3-Chloro-5-(3-nitrophenoxy)pyridine

HRID 1532013Notes

Reaction equation

HRID 1532013 reaction equation
[OH-].[K+].[N+:3]([C:6]1[CH:7]=[C:8]([OH:12])[CH:9]=[CH:10][CH:11]=1)([O-:5])=[O:4].[Cl:13][C:14]1[CH:15]=[N:16][CH:17]=[C:18](Cl)[CH:19]=1>O.CCOC(C)=O.CN1CCCC1=O.C1(C)C=CC=CC=1>[N+:3]([C:6]1[CH:7]=[C:8]([CH:9]=[CH:10][CH:11]=1)[O:12][C:18]1[CH:19]=[C:14]([Cl:13])[CH:15]=[N:16][CH:17]=1)([O-:5])=[O:4]

Participants

8

Reactant 3

HCID 111373-NitrophenolHCID 14797Potassium HydroxideHCID 171533,5-Dichloropyridine

Product 1

HCID 229938583-Chloro-5-(3-nitrophenoxy)pyridine

Reagents, catalysts & solvents 4

HCID 962WaterSolvent2×HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolvent2×

Conditions

Temperature
110 °C

Procedure

The title compound was prepared using methods described in U.S. Pat. No. 3,576,616. Briefly, to a 16.5M solution of KOH (2.2 g, 39.6 mmol) in water was added 3-nitrophenol (5 g, 36 mmol) followed by N-methylpyrrolidinone (11 mL) and toluene (3.6 mL). The resulting mixture was heated to 110° C. and water was removed azeotropically using a Dean-Stark trap. Excess toluene was removed and collected in the trap followed by the addition of N-methylpyrrolidinone (18 mL) and 3,5-dichloropyridine (10.66 g, 72 mmol, Aldrich) and the mixture was stirred for 5 hr at 160° C. The temperature was then increased to 200° C. and the mixture was stirred for an additional 15 hr. The crude reaction mixture was cooled, water (100 mL) was added followed by EtOAc (100 mL). The mixture was filtered through a pad of Celite®, the phases were separated, and the aqueous phase was extracted 3× with EtOAc (100 mL). The organic phases were combined and washed twice with water (100 mL), once with brine (100 mL), dried over Na2SO4, and concentrated under vacuum. The crude solid was purified by chromatography (10-25% EtOAc in hexanes as eluant) to provide 3.8 g (42%) of product as an orange solid.

Workup

  1. customwater was removed azeotropically
  2. customExcess toluene was removed
  3. customcollected in the trap
  4. temperatureThe temperature was then increased to 200° C.
  5. stirringthe mixture was stirred for an additional 15 hr
  6. customThe crude reaction mixture
  7. temperaturewas cooled
  8. filtrationThe mixture was filtered through a pad of Celite®
  9. customthe phases were separated
  10. extractionthe aqueous phase was extracted 3× with EtOAc (100 mL)
  11. washwashed twice with water (100 mL), once with brine (100 mL)
  12. dry with materialdried over Na2SO4
  13. concentrationconcentrated under vacuum
  14. customThe crude solid was purified by chromatography (10-25% EtOAc in hexanes as eluant)

Sources & evidence

ORD record
ord-61cde609633d4f72ae53fe9a865b61f2
Source dataset
uspto-grants-2001_03
Patent number
US06200995B1

Reaction notes

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