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

HRID 2066175Notes

Reaction equation

HRID 2066175 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

4-Chloropyridine-2-carboxylic acid methyl ester (30 g) and 2-fluoro-4-nitrophenol (41.2 g) were dissolved in chlorobenzene (24 ml), followed by stirring under a nitrogen atmosphere at 120° C. for 4 hr. The reaction mixture was allowed to cool down to room temperature, methanol (100 ml) was added, and stirred for 30 min. The solvent was removed under reduced pressure, then the resultant residue was partitioned between ethyl acetate (300 ml) and a 1N aqueous solution of sodium hydroxide (150 ml). The separated organic layer was washed with a 1N aqueous solution of sodium hydroxide (100 ml) and brine (150 ml) and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure, ethanol (200 ml) was added to the resultant residue, followed by stirring for 30 min. The solid was collected by filtration and 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, the resultant solid was combined to the solid above to provide 4-(2-fluoro-4-nitrophenoxy)pyridine-2-carboxylic acid methyl ester as a pale brown solid (20.0 g, 40.0%).

Workup

  1. temperatureto cool down to room temperature
  2. stirringstirred for 30 min
  3. customThe solvent was removed under reduced pressure
  4. customthe resultant residue was partitioned between ethyl acetate (300 ml)
  5. washThe separated organic layer was washed with a 1N aqueous solution of sodium hydroxide (100 ml) and brine (150 ml)
  6. dry with materialdried over anhydrous sodium sulfate
  7. customThe solvent was removed under reduced pressure, ethanol (200 ml)
  8. additionwas added to the resultant residue
  9. stirringby stirring for 30 min
  10. filtrationThe solid was collected by filtration
  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-d40fcaee547744bd81d3c87cf97f560d
Source dataset
uspto-grants-2012_10
Patent number
US08288538B2

Reaction notes

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