4-Amino-2,5-difluorophenol → HCID 66339751, compound

HRID 1045998Notes

Reaction equation

HRID 1045998 reaction equation
[NH2:1][C:2]1[C:7]([F:8])=[CH:6][C:5]([OH:9])=[C:4]([F:10])[CH:3]=1.CC(C)([O-])C.[K+].Cl[C:18]1[C:23]([I:24])=[CH:22][N:21]=[CH:20][N:19]=1>CN(C=O)C>[F:8][C:7]1[CH:6]=[C:5]([O:9][C:18]2[C:23]([I:24])=[CH:22][N:21]=[CH:20][N:19]=2)[C:4]([F:10])=[CH:3][C:2]=1[NH2:1]

Participants

5

Reactant 3

HCID 27787624-Amino-2,5-difluorophenolHCID 112302044-Chloro-5-iodopyrimidineHCID 23665647Potassium tert-butoxide

Product 1

HCID 66339751HCID 66339751, compoundYield 36.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 4-amino-2,5-difluorophenol (0.190 g, 1.310 mmol) in DMF (10 mL) was added potassium tert-butoxide (0.168 g, 1.497 mmol). The mixture was stirred at RT for 30 min. 4-Chloro-5-iodopyrimidine (0.30 g, 1.248 mmol) was added and the reaction mixture was heated at 80° C. overnight. The reaction mixture was quenched with water and the solution was extracted with EtOAc (3×). The organic solution was washed with 5% aqueous lithium chloride solution and brine. The organics were dried over MgSO4, filtered, and concentrated. The crude was purified by silica gel column chromatography (10% to 50% EtOAc/hexane) to obtain 2,5-difluoro-4-(5-iodopyrimidin-4-yloxy)benzenamine (160 mg, 36.7% yield) which was used for the next reaction. MS (ESI) m/z: 349.9 (M+H+).

Workup

  1. temperaturethe reaction mixture was heated at 80° C. overnight
  2. customThe reaction mixture was quenched with water
  3. extractionthe solution was extracted with EtOAc (3×)
  4. washThe organic solution was washed with 5% aqueous lithium chloride solution and brine
  5. dry with materialThe organics were dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude was purified by silica gel column chromatography (10% to 50% EtOAc/hexane)

Sources & evidence

ORD record
ord-7913d35f78e540ebb8a4404283661ac1
Source dataset
uspto-grants-2013_10
Patent number
US08569319B2

Reaction notes

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