2-Fluoro-4-nitrophenol → 2-Amino-4-(2-fluoro-4-nitrophenoxy)pyridine

HRID 2066169Notes

Reaction equation

HRID 2066169 reaction equation
[NH2:1][C:2]1[CH:7]=[C:6](Cl)[CH:5]=[CH:4][N:3]=1.[F:9][C:10]1[CH:15]=[C:14]([N+:16]([O-:18])=[O:17])[CH:13]=[CH:12][C:11]=1[OH:19].C(N(CC)C(C)C)(C)C>CN1CCCC1=O>[NH2:1][C:2]1[CH:7]=[C:6]([O:19][C:11]2[CH:12]=[CH:13][C:14]([N+:16]([O-:18])=[O:17])=[CH:15][C:10]=2[F:9])[CH:5]=[CH:4][N:3]=1

Participants

5

Reactant 3

HCID 98252-Fluoro-4-nitrophenolHCID 81531DiisopropylethylamineHCID 5818662-Amino-4-chloropyridine

Product 1

HCID 231531982-Amino-4-(2-fluoro-4-nitrophenoxy)pyridineYield 20%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
160 °C

Procedure

2-Amino-4-chloropyridine (8.00 g) was dissolved in N-methylpyrrolidone (65 ml), and 2-fluoro-4-nitrophenol (19.55 g) and N,N-diisopropylethylamine (43.36 ml) were added thereto, followed by stirring at 160° C. for 41 hr. The reaction mixture was allowed to cool down to room temperature, and was partitioned between ethyl acetate-tetrahydrofuran (1:1) and a 2N aqueous solution of sodium hydroxide. The organic layer was washed with water and brine in this order. The aqueous layer was re-extracted with ethyl acetate, and the combined organic layer was dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure, the residue was purified by silica gel column chromatography (eluent; hexane:ethyl acetate=1:2, then ethyl acetate). Fractions containing the target compound were concentrated, and crystals were precipitated by addition of ethyl acetate to the residue. The crystals were collected by filtration and dried under aeration to provide the titled compound as opalescent crystals (3.02 g, 20%).

Workup

  1. temperatureto cool down to room temperature
  2. customwas partitioned between ethyl acetate-tetrahydrofuran (1:1)
  3. washThe organic layer was washed with water and brine in this order
  4. extractionThe aqueous layer was re-extracted with ethyl acetate
  5. dry with materialthe combined organic layer was dried over anhydrous sodium sulfate
  6. customThe solvent was removed under reduced pressure
  7. customthe residue was purified by silica gel column chromatography (eluent
  8. additionFractions containing the target compound
  9. concentrationwere concentrated
  10. customcrystals were precipitated by addition of ethyl acetate to the residue
  11. filtrationThe crystals were collected by filtration
  12. customdried under aeration

Sources & evidence

ORD record
ord-8e15143750ff470181e0aa6b5f3ace78
Source dataset
uspto-grants-2012_10
Patent number
US08288538B2

Reaction notes

Loading…