2-Aminophenol → 2-(4-Fluoro-3-nitrophenyl)benzoxazole

HRID 7695

Reaction equation

HRID 7695 reaction equation
[F:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=O)=[CH:4][C:3]=1[N+:11]([O-:13])=[O:12].S(Cl)(Cl)=O.[NH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=1O.C(N(C(C)C)CC)(C)C.C1(C)C=CC(S(O)(=O)=O)=CC=1>C1COCC1.C1(C)C=CC=CC=1>[F:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]2[O:8][C:20]3[CH:21]=[CH:22][CH:23]=[CH:24][C:19]=3[N:18]=2)=[CH:4][C:3]=1[N+:11]([O-:13])=[O:12]

Participants

8

Reactant 5

HCID 58012-AminophenolHCID 6101p-Toluenesulfonic acidHCID 24386Thionyl ChlorideHCID 679874-Fluoro-3-nitrobenzoic acidHCID 81531Diisopropylethylamine

Product 1

HCID 219909702-(4-Fluoro-3-nitrophenyl)benzoxazole

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 4-fluoro-3-nitrobenzoic acid (2.1 g, 11.3 mmol) and thionyl chloride (20 mL) was refluxed for 3 h and then cooled to rt. The excess thionyl chloride was removed and the residue dissolved in 10 mL of THF was added to a cooled (0° C.) solution of 2-aminophenol (1.24 g, 11.3 mmol) and diisopropylethylamine (2.4 mL, 13.6 mmol) in anhydrous THF (20 mL). The resulting mixture was refluxed for 4 h and then cooled to rt. The solvent was removed and p-toluenesulfonic acid (8.63 g, 45.4 mmol) and toluene (50 mL) were added to afford a dark mixture that was refluxed overnight. The solvent was removed and the crude was purified by flash chromatography on silica gel eluting with hexanes:CH2Cl2 (1:5) to afford 2-(4-fluoro-3-nitrophenyl)-1,3-benzoxazole as a colorless solid.

Workup

  1. temperaturewas refluxed for 3 h
  2. customThe excess thionyl chloride was removed
  3. dissolutionthe residue dissolved in 10 mL of THF
  4. additionwas added to
  5. temperatureThe resulting mixture was refluxed for 4 h
  6. temperaturecooled to rt
  7. customThe solvent was removed
  8. customto afford a dark mixture that
  9. temperaturewas refluxed overnight
  10. customThe solvent was removed
  11. customthe crude was purified by flash chromatography on silica gel eluting with hexanes:CH2Cl2 (1:5)

Sources & evidence

ORD record
ord-66860e715ea94b10b846f7aa9de156cf
Source dataset
uspto-grants-2006_08
Patent number
US07087601B2

Linked notes

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