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

HRID 2066171Notes

Reaction equation

HRID 2066171 reaction equation
Cl[C:2]1[CH:7]=[CH:6][N:5]=[C:4]([C:8]([O:10][CH2:11][CH3:12])=[O:9])[CH:3]=1.[F:13][C:14]1[CH:15]=[C:16]([OH:23])[CH:17]=[CH:18][C:19]=1[N+:20]([O-:22])=[O:21].ClC1C=CC=CC=1.C(=O)([O-])O.[Na+]>C(OCC)(=O)C>[F:13][C:14]1[CH:15]=[C:16]([CH:17]=[CH:18][C:19]=1[N+:20]([O-:22])=[O:21])[O:23][C:2]1[CH:7]=[CH:6][N:5]=[C:4]([C:8]([O:10][CH2:11][CH3:12])=[O:9])[CH:3]=1

Participants

6

Reactant 4

HCID 7964ChlorobenzeneHCID 516892Sodium BicarbonateHCID 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

To ethyl 4-chloropyridine-2-carboxylate (19.4 g) were added 3-fluoro-4-nitrophenol (24.7 g) and chlorobenzene (7.0 ml), followed by heating and stirring under a nitrogen atmosphere at 120° C. for 4 hr. The reaction mixture was allowed to cool down to room temperature. Ethyl acetate (400 ml) and a saturated aqueous solution of sodium hydrogencarbonate (400 ml) were added thereto, followed by stirring at room temperature for 27 hr. Stirring was stopped and the aqueous layer was separated. To the organic layer was added again a saturated aqueous solution of sodium hydrogencarbonate, followed by stirring at room temperature for 2 days. Stirring was stopped and the aqueous layer was separated. The aqueous layer was 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 concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent; heptane:ethyl acetate=2:1, 1:1, then ethyl acetate). Fractions containing the target compound were concentrated to provide the titled compound as a brown oil (12.9 g, 40.2%).

Workup

  1. temperatureby heating
  2. temperatureto cool down to room temperature
  3. stirringby stirring at room temperature for 27 hr
  4. stirringStirring
  5. customthe aqueous layer was separated
  6. additionTo the organic layer was added again a saturated aqueous solution of sodium hydrogencarbonate
  7. stirringby stirring at room temperature for 2 days
  8. stirringStirring
  9. customthe aqueous layer was separated
  10. extractionThe aqueous layer was extracted with ethyl acetate (300 ml)
  11. washwashed with brine
  12. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  13. concentrationconcentrated under reduced pressure
  14. customThe residue was purified by silica gel column chromatography (eluent
  15. additionFractions containing the target compound
  16. concentrationwere concentrated

Sources & evidence

ORD record
ord-b3bc306dc3c7448196b79c3b5ca31bfb
Source dataset
uspto-grants-2012_10
Patent number
US08288538B2

Reaction notes

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