Methanol → 4-(2-Fluoro-4-nitrophenoxy)pyridine-2-carboxylic acid methyl ester

HRID 492836Notes

Reaction equation

HRID 492836 reaction equation
[CH3:1][O:2][C:3]([C:5]1[CH:10]=[C:9](Cl)[CH:8]=[CH:7][N:6]=1)=[O:4].[F:12][C:13]1[CH:18]=[C:17]([N+:19]([O-:21])=[O:20])[CH:16]=[CH:15][C:14]=1[OH:22].CO>ClC1C=CC=CC=1>[CH3:1][O:2][C:3]([C:5]1[CH:10]=[C:9]([O:22][C:14]2[CH:15]=[CH:16][C:17]([N+:19]([O-:21])=[O:20])=[CH:18][C:13]=2[F:12])[CH:8]=[CH:7][N:6]=1)=[O:4]

Participants

5

Reactant 3

HCID 887MethanolHCID 98252-Fluoro-4-nitrophenolHCID 820890Methyl 4-Chloropicolinate

Product 1

HCID 574708574-(2-Fluoro-4-nitrophenoxy)pyridine-2-carboxylic acid methyl esterYield 40%

Reagents, catalysts & solvents 1

HCID 7964ChlorobenzeneSolvent

Conditions

Temperature
120 °C

Procedure

After dissolving 4-chloropyridine-2-carboxylic acid methyl ester (30 g) and 2-fluoro-4-nitrophenol (41.2 g) in chlorobenzene (24 ml), the reaction mixture was stirred for 4 hours at 120° C. under a nitrogen atmosphere. The reaction mixture was brought to room temperature, methanol (100 ml) was added, and the mixture was stirred for 30 minutes. After distilling off the solvent under reduced pressure, the resultant residue was partitioned between ethyl acetate (300 ml) and 1N aqueous sodium hydroxide (150 ml). The separated organic layer was washed with 1N aqueous sodium hydroxide (100 ml) and brine (150 ml) and then dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and then ethanol (200 ml) was added to the resultant residue and the mixture was stirred for 30 minutes. After filtering the solid, the filtrate was purified by silica gel column chromatography (YMC, SIL-60-400/230W, eluent; heptane:ethyl acetate=1:1). Fractions containing the target compound were concentrated under reduced pressure, and the obtained solid was combined with the previously obtained solid to provide 4-(2-fluoro-4-nitrophenoxy)pyridine-2-carboxylic acid methyl ester (20.0 g, 40.0%) as a pale brown solid.

Workup

  1. customwas brought to room temperature
  2. stirringthe mixture was stirred for 30 minutes
  3. distillationAfter distilling off the solvent under reduced pressure
  4. customthe resultant residue was partitioned between ethyl acetate (300 ml) and 1N aqueous sodium hydroxide (150 ml)
  5. washThe separated organic layer was washed with 1N aqueous sodium hydroxide (100 ml) and brine (150 ml)
  6. dry with materialdried over anhydrous sodium sulfate
  7. distillationThe solvent was distilled off under reduced pressure
  8. additionethanol (200 ml) was added to the resultant residue
  9. stirringthe mixture was stirred for 30 minutes
  10. filtrationAfter filtering the solid
  11. customthe filtrate was purified by silica gel column chromatography (YMC, SIL-60-400/230W, eluent; heptane:ethyl acetate=1:1)
  12. additionFractions containing the target compound
  13. concentrationwere concentrated under reduced pressure

Sources & evidence

ORD record
ord-ff699ce6e2594ba59abfb91fe414d774
Source dataset
uspto-grants-2009_05
Patent number
US07531532B2

Reaction notes

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