Calcium Chloride → 3-Fluoro-4-{[3-(1-methyl-1H-pyrazol-5-yl)biphenyl-4-yl]oxy}aniline

HRID 1619645Notes

Reaction equation

HRID 1619645 reaction equation
[F:1][C:2]1[CH:26]=[C:25]([N+:27]([O-])=O)[CH:24]=[CH:23][C:3]=1[O:4][C:5]1[CH:10]=[CH:9][C:8]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[CH:7][C:6]=1[C:17]1[N:21]([CH3:22])[N:20]=[CH:19][CH:18]=1.[Cl-].[Cl-].[Ca+2]>C(O)C.O.[Fe]>[F:1][C:2]1[CH:26]=[C:25]([CH:24]=[CH:23][C:3]=1[O:4][C:5]1[CH:10]=[CH:9][C:8]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[CH:7][C:6]=1[C:17]1[N:21]([CH3:22])[N:20]=[CH:19][CH:18]=1)[NH2:27]

Participants

6

Reactant 2

HCID 5284359Calcium ChlorideHCID 580422745-[4-(2-Fluoro-4-nitrophenoxy)biphenyl-3-yl]-1-methyl-1H-pyrazole

Product 1

HCID 580423493-Fluoro-4-{[3-(1-methyl-1H-pyrazol-5-yl)biphenyl-4-yl]oxy}anilineYield 84%

Reagents, catalysts & solvents 3

HCID 23925IronCatalystHCID 702EthanolSolventHCID 962WaterSolvent

Procedure

5-[4-(2-Fluoro-4-nitrophenoxy)biphenyl-3-yl]-1-methyl-1H-pyrazole (Preparation 29, 870 mg, 2.33 mmol) was dissolved in ethanol (8 mL) and water (2 mL). Iron powder (624 mg, 11.17 mmol) and CaCl2 (248 mg, 2.33 mmol) were then added and the reaction mixture was refluxed for 3 hours. After filtration through Celite™, the filtrate was concentrated in vacuo. The residue was partitioned between dichloromethane and water. The organic layer was separated, washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue was purified by silica gel column chromatography (100-200 mesh silica gel, 15% ethyl acetate in hexane) to afford the title compound (700 mg, 84%).

Workup

  1. temperaturethe reaction mixture was refluxed for 3 hours
  2. filtrationAfter filtration through Celite™
  3. concentrationthe filtrate was concentrated in vacuo
  4. customThe residue was partitioned between dichloromethane and water
  5. customThe organic layer was separated
  6. washwashed with brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe residue was purified by silica gel column chromatography (100-200 mesh silica gel, 15% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-1e11bcb1f2274071be1bedf4ec818b52
Source dataset
uspto-grants-2014_07
Patent number
US08772293B2

Reaction notes

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