Hydrochloric Acid → 2-Fluoro-4-(trifluoroMethoxy)aniline

HRID 2089820Notes

Reaction equation

HRID 2089820 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([O:8][C:9]([F:12])([F:11])[F:10])=[CH:4][C:3]=1[F:13].C(=[NH:27])(C1C=CC=CC=1)C1C=CC=CC=1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.CC(C)([O-])C.[Na+].Cl.[OH-].[Na+]>O1CCOCC1.C1COCC1.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]>[F:13][C:3]1[CH:4]=[C:5]([O:8][C:9]([F:12])([F:11])[F:10])[CH:6]=[CH:7][C:2]=1[NH2:27]

Participants

10

Reactant 6

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 136809Benzophenone imineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 220652111-Bromo-2-fluoro-4-(trifluoromethoxy)benzeneHCID 23676156Sodium t-butoxide

Product 1

HCID 144393042-Fluoro-4-(trifluoroMethoxy)anilineYield 85%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8028TetrahydrofuranSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 4-bromo-3-fluoro(trifluoromethoxy)benzene (6.6 g, 26 mmol), benzophenone imine (6.4 mL, 38 mmol), Pd2(dba)3 (0.58 g, 0.64 mmol), Xantphos (1.5 g, 2.6 mmol) and sodium tert-butoxide (3.7 g, 38 mmol) in 1,4-dioxane (120 mL) was stirred at 100° C. under N2 atmosphere for 5 h. After stirring at room temperature overnight, the mixture was concentrated under reduced pressure. The residue was partitioned between AcOEt and water. The organic layer was washed with brine, dried over MgSO4, filtered and concentrated under reduced pressure. The residue was chromatographed on silica gel (0/100-5/95 AcOEt/hexane) to give a yellow oil. The residual oil was dissolved in THF (150 mL), and 1 M HCl aqueous solution (50 mL) was added to the mixture. After stirring at room temperature for 1 h, the mixture was basified with 8 M NaOH aqueous solution and extracted with diethyl ether. The organic layer was washed with brine, dried over MgSO4, filtered and concentrated under reduced pressure. The residue was chromatographed on silica gel (0/100-5/95 AcOEt/hexane) to give the title compound (4.2 g, 85% yield) as a pale yellow oil: 1H NMR (300 MHz, DMSO-d6): δ ppm 5.36 (2H, s), 6.75-6.85 (1H, m), 6.89-6.94 (1H, m), 7.12 (1H, dd, J=11.7, 2.3 Hz).

Workup

  1. stirringAfter stirring at room temperature overnight
  2. concentrationthe mixture was concentrated under reduced pressure
  3. customThe residue was partitioned between AcOEt and water
  4. washThe organic layer was washed with brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was chromatographed on silica gel (0/100-5/95 AcOEt/hexane)
  9. customto give a yellow oil
  10. stirringAfter stirring at room temperature for 1 h
  11. extractionextracted with diethyl ether
  12. washThe organic layer was washed with brine
  13. dry with materialdried over MgSO4
  14. filtrationfiltered
  15. concentrationconcentrated under reduced pressure
  16. customThe residue was chromatographed on silica gel (0/100-5/95 AcOEt/hexane)

Sources & evidence

ORD record
ord-19ac17e03f9e4c569b755c7861195bd8
Source dataset
uspto-grants-2013_05
Patent number
US08435995B2

Reaction notes

Loading…