Benzophenone imine → 3,5-Difluoroaniline

HRID 348534Notes

Reaction equation

HRID 348534 reaction equation
CC(C)([O-])C.[Na+].Cl[C:8]1[CH:13]=[C:12]([F:14])[CH:11]=[C:10]([F:15])[CH:9]=1.C(=[NH:29])(C1C=CC=CC=1)C1C=CC=CC=1>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[F:15][C:10]1[CH:9]=[C:8]([CH:13]=[C:12]([F:14])[CH:11]=1)[NH2:29]

Participants

6

Reactant 3

HCID 136809Benzophenone imine2×HCID 137000Benzene, 1-chloro-3,5-difluoro-HCID 23676156Sodium t-butoxide

Product 1

HCID 965953,5-DifluoroanilineYield 89%

Reagents, catalysts & solvents 2

HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Procedure

A 4-neck, 500 mL flask was equipped with a mechanical stirrer, a glass stopper, a rubber septum and a condenser with an inert gas inlet. To this flask was added, in order, tris(dibenzylideneacetone)dipalladium (0) (Pd2(dba)3) (25 mg, 0.01 mol %), 1,1′-bis(diphenylphosphino)ferrocene (dppf) (46 mg, 0.03 mol %), sodium tert-butoxide (37 g, 1.4 eq, xylenes (90 mL), 1-chloro-3,5-difluorobenzene (49.2 g, 0.33 mol) and benzophenone imine (50 g, 0.28 mol). The mixture was refluxed for 8 hours until GC analysis confirmed that the benzophenone imine had been consumed. The reaction mixture was cooled slightly, and 150 mL of 2M HCl was added slowly to the reaction mixture with some gas evolution and the mixture was refluxed with sufficient agitation for 45 minutes. While still warm, the reaction mixture was put in a separatory funnel and the aqueous layer was collected. An additional 90 mL of xylenes was added to the separatory funnel and the organic layer was washed with 4×100 mL 1M HCl. The acidic fractions were combined and made alkaline with aqueous conc ammonium hydroxide. The free amine was extracted with 250 mL methyl tert-butyl ether. The organic layer was dried over magnesium sulfate and concentrated in vacuo to yield the expected product in 89% yield.

Workup

  1. customA 4-neck, 500 mL flask was equipped with a mechanical stirrer
  2. temperatureThe mixture was refluxed for 8 hours until GC analysis
  3. customhad been consumed
  4. temperatureThe reaction mixture was cooled slightly
  5. addition150 mL of 2M HCl was added slowly to the reaction mixture with some gas evolution
  6. temperaturethe mixture was refluxed with sufficient agitation for 45 minutes
  7. temperatureWhile still warm
  8. customthe reaction mixture was put in a separatory funnel
  9. customthe aqueous layer was collected
  10. additionAn additional 90 mL of xylenes was added to the separatory funnel
  11. washthe organic layer was washed with 4×100 mL 1M HCl
  12. extractionThe free amine was extracted with 250 mL methyl tert-butyl ether
  13. dry with materialThe organic layer was dried over magnesium sulfate
  14. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-68c6ef21d4fd4f6a853efdd94a8c333a
Source dataset
uspto-grants-2007_02
Patent number
US07176334B2

Reaction notes

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