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

HRID 2116560Notes

Reaction equation

HRID 2116560 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 reactions 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 Na2O4, 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. temperatureThe crude reactions mixture was cooled
  7. filtrationThe mixture was filtered through a pad of Celite®
  8. customthe phases were separated
  9. extractionthe aqueous phase was extracted 3× with EtOAc (100 mL)
  10. washwashed twice with water (100 mL), once with brine (100 mL)
  11. customdried over Na2O4
  12. concentrationconcentrated under vacuum
  13. customThe crude solid was purified by chromatography (10-25% EtOAc in hexanes as eluant)

Sources & evidence

ORD record
ord-6fa8ea0624504dde812ad920b345ceb3
Source dataset
uspto-grants-2008_10
Patent number
US07439242B2

Reaction notes

Loading…