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

HRID 388490

Reaction equation

HRID 388490 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+].[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 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

To ethyl 4-chloropyridine-2-carboxylate (19.4 g) were added 3-fluoro-4-nitrophenol (24.7 g) and chlorobenzene (7.0 ml), and the % mixture was stirred and heated at 120° C. under a nitrogen atmosphere for 4 hours. The reaction mixture was cooled to room temperature. After adding ethyl acetate (400 ml) and a saturated aqueous solution of sodium carbonate (400 ml), the mixture was further stirred at room temperature for 27 hours. Stirring was suspended and the aqueous layer was separated off. A saturated aqueous solution of sodium carbonate was further added to the organic layer and the mixture was, stirred at room temperature for 2 days. Stirring was suspended, and the aqueous layer was separated off. 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 to 1:1, then ethyl acetate). The fractions containing the target compound were concentrated to give the title compound as a brown oil (12.9 g, 40.2%).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. stirringStirring
  3. customthe aqueous layer was separated off
  4. additionA saturated aqueous solution of sodium carbonate was further added to the organic layer
  5. stirringstirred at room temperature for 2 days
  6. stirringStirring
  7. customthe aqueous layer was separated off
  8. extractionThe aqueous layer was 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. additionThe fractions containing the target compound
  14. concentrationwere concentrated

Sources & evidence

ORD record
ord-455855a654e94adc9a4ee648fb9d71be
Source dataset
uspto-grants-2013_02
Patent number
US08377938B2

Linked notes

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