Chlorobenzene → Ethyl 4-(3-fluoro-4-nitrophenoxy)pyridine-2-carboxylate

HRID 492842

Reaction equation

HRID 492842 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([OH:11])[CH:5]=[CH:6][C:7]=1[N+:8]([O-:10])=[O:9].ClC1C=CC=CC=1.Cl[C:20]1[CH:25]=[CH:24][N:23]=[C:22]([C:26]([O:28][CH2:29][CH3:30])=[O:27])[CH:21]=1.C(=O)([O-])[O-].[Na+].[Na+]>C(OCC)(=O)C>[F:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][C:7]=1[N+:8]([O-:10])=[O:9])[O:11][C:20]1[CH:25]=[CH:24][N:23]=[C:22]([C:26]([O:28][CH2:29][CH3:30])=[O:27])[CH:21]=1

Participants

6

Reactant 4

HCID 7964ChlorobenzeneHCID 10340Sodium CarbonateHCID 5209483-Fluoro-4-nitrophenolHCID 130153594-Chloropyridine-2-carboxylic acid ethyl ester

Product 1

HCID 23153599Ethyl 4-(3-fluoro-4-nitrophenoxy)pyridine-2-carboxylateYield 40.3%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

After adding 3-fluoro-4-nitrophenol (24.7 g) and chlorobenzene (7.0 ml) to ethyl 4-chloropyridine-2-carboxylate (19.4 g), the mixture was heated and stirred for 4 hours at 120° C. under a nitrogen atmosphere. The reaction mixture was then cooled to room temperature. Ethyl acetate (400 ml) and saturated aqueous sodium carbonate (400 ml) were added thereto and the mixture was stirred for 27 hours at room temperature. The stirring was paused and the aqueous layer was separated. Saturated aqueous sodium carbonate was again added to the organic layer, and the mixture was stirred at room temperature for 2 days. The stirring was again paused and the aqueous layer was separated. The aqueous layer was then extracted with ethyl acetate (300 ml). The organic layers were combined and washed with brine. The organic layer was dried over anhydrous sodium sulfate and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent; heptane:ethyl acetate=2:1 to 1:1, then ethyl acetate). Fractions containing the target compound were concentrated to provide the title compound (12.9 g, 40.2%) as a brown oil.

Workup

  1. temperaturethe mixture was heated
  2. temperatureThe reaction mixture was then cooled to room temperature
  3. stirringthe mixture was stirred for 27 hours at room temperature
  4. customthe aqueous layer was separated
  5. additionSaturated aqueous sodium carbonate was again added to the organic layer
  6. stirringthe mixture was stirred at room temperature for 2 days
  7. customthe aqueous layer was separated
  8. extractionThe aqueous layer was then extracted with ethyl acetate (300 ml)
  9. washwashed with brine
  10. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  11. concentrationconcentrated under reduced pressure
  12. customThe residue was purified by silica gel column chromatography (eluent
  13. additionFractions containing the target compound
  14. concentrationwere concentrated

Sources & evidence

ORD record
ord-97751f675ce34cf6b337793cace54415
Source dataset
uspto-grants-2009_05
Patent number
US07531532B2

Linked notes

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