2-Fluoro-4-nitrophenol → 4-Amino-6-(2-fluoro-4-nitrophenoxy)pyrimidine

HRID 2066187Notes

Reaction equation

HRID 2066187 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([N+:8]([O-:10])=[O:9])[CH:5]=[CH:4][C:3]=1[OH:11].[H-].[Na+].[NH2:14][C:15]1[CH:20]=[C:19](Cl)[N:18]=[CH:17][N:16]=1.[OH-].[Na+]>CS(C)=O>[F:1][C:2]1[CH:7]=[C:6]([N+:8]([O-:10])=[O:9])[CH:5]=[CH:4][C:3]=1[O:11][C:19]1[N:18]=[CH:17][N:16]=[C:15]([NH2:14])[CH:20]=1

Participants

6

Reactant 4

HCID 98252-Fluoro-4-nitrophenolHCID 14798Sodium HydroxideHCID 24758Sodium hydrideHCID 2380124-Amino-6-chloropyrimidine

Product 1

HCID 231530124-Amino-6-(2-fluoro-4-nitrophenoxy)pyrimidineYield 16.1%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
120 °C

Procedure

2-Fluoro-4-nitrophenol (1.736 g) was dissolved in dimethyl sulfoxide (10 ml), and sodium hydride (400 mg) was added thereto, followed by stirring for 20 min. Then, 4-Amino-6-chloropyrimidine (648 mg) was added thereto and stirred at 100° C. for 45 min. The reaction mixture was heated up to 120° C. and stirred for 1 hr 25 min. The reaction mixture was then heated up to 140° C. and stirred overnight. The reaction mixture was allowed to cool down to room temperature, a 1N aqueous solution of sodium hydroxide (10 ml) was added thereto and stirred, then extracted with ethyl acetate. The organic layer was washed with a 1N aqueous solution of sodium hydroxide, water and brine in this order, and dried over anhydrous sodium sulfate. The solvent was concentrated under reduced pressure to give residue, which was purified by silica gel column chromatography (eluent; hexane:ethyl acetate=1:2). The solvent was concentrated under reduced pressure, the resultant residue was suspended in diethyl ether (7 ml)-hexane (3.5 ml). The solid was collected by filtration and dried under aeration to provide the titled compound as pale brown powder (201 mg, 16.0%).

Workup

  1. stirringstirred at 100° C. for 45 min
  2. stirringstirred for 1 hr 25 min
  3. temperatureThe reaction mixture was then heated up to 140° C.
  4. stirringstirred overnight
  5. temperatureto cool down to room temperature
  6. stirringstirred
  7. extractionextracted with ethyl acetate
  8. washThe organic layer was washed with a 1N aqueous solution of sodium hydroxide, water and brine in this order
  9. dry with materialdried over anhydrous sodium sulfate
  10. concentrationThe solvent was concentrated under reduced pressure
  11. customto give residue, which
  12. customwas purified by silica gel column chromatography (eluent; hexane:ethyl acetate=1:2)
  13. concentrationThe solvent was concentrated under reduced pressure
  14. filtrationThe solid was collected by filtration
  15. customdried under aeration

Sources & evidence

ORD record
ord-80f299c2b1f3491ab554cb0c54f5ef68
Source dataset
uspto-grants-2012_10
Patent number
US08288538B2

Reaction notes

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