Ethyl Acetate → 2-Amino-4-(2-fluoro-4-nitrophenoxy)pyridine

HRID 492663Notes

Reaction equation

HRID 492663 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.C(OCC)(=O)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

6

Reactant 4

HCID 8857Ethyl AcetateHCID 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 then 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 hrs. The reaction mixture was cooled down to room temperature, and partitioned between ethyl acetate-tetrahydrofuran (1:1) and a 2 N aqueous solution of sodium hydroxide. The organic layer was washed with water and brine in this order. The aqueous layer was extracted again with ethyl acetate. The combined organic layer was dried over anhydrous sodium sulfate. The solvent was evaporated under a reduced pressure to give a residue, which was purified by silica gel column chromatography (eluent; hexane:ethyl acetate=1:2, then ethyl acetate). Fractions containing the target compound were concentrated to provide a residue, to which ethyl acetate was added to precipitate crystals. The crystals were filtered, and dried under aeration to provide the titled compound (3.02 g, 20%) as opaline crystals.

Workup

  1. temperatureThe reaction mixture was cooled down to room temperature
  2. custompartitioned between ethyl acetate-tetrahydrofuran (1:1)
  3. washThe organic layer was washed with water and brine in this order
  4. extractionThe aqueous layer was extracted again with ethyl acetate
  5. dry with materialThe combined organic layer was dried over anhydrous sodium sulfate
  6. customThe solvent was evaporated under a reduced pressure
  7. customto give a residue, which
  8. customwas purified by silica gel column chromatography (eluent
  9. additionFractions containing the target compound
  10. concentrationwere concentrated
  11. customto provide a residue
  12. customto precipitate crystals
  13. filtrationThe crystals were filtered
  14. customdried under aeration

Sources & evidence

ORD record
ord-8494741063f44030979ed402d7161b08
Source dataset
uspto-grants-2009_05
Patent number
US07531532B2

Reaction notes

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