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

HRID 492719Notes

Reaction equation

HRID 492719 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.C(OCC)C.CCCCCC>[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

8

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 3

HCID 679Dimethyl SulfoxideSolventHCID 3283Diethyl EtherSolventHCID 8058HexaneSolvent

Conditions

Temperature
120 °C

Procedure

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

Workup

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

Sources & evidence

ORD record
ord-67da64e092a24d2d98f2a8a8ea00d05c
Source dataset
uspto-grants-2009_05
Patent number
US07531532B2

Reaction notes

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