3-Iodophenol → HCID 58674384, compound

HRID 1994155Notes

Reaction equation

HRID 1994155 reaction equation
C([O-])(O)=O.[Na+].[Cl:6][C:7]1[CH:12]=[CH:11][C:10]([NH:13][C:14](=[O:18])[C:15]([CH3:17])=[CH2:16])=[CH:9][C:8]=1[C:19]([F:22])([F:21])[F:20].I[C:24]1[CH:25]=[C:26]([OH:30])[CH:27]=[CH:28][CH:29]=1>C(#N)C.CC([O-])=O.CC([O-])=O.[Pd+2]>[Cl:6][C:7]1[CH:12]=[CH:11][C:10]([NH:13][C:14](=[O:18])/[C:15](/[CH3:17])=[CH:16]/[C:24]2[CH:29]=[CH:28][CH:27]=[C:26]([OH:30])[CH:25]=2)=[CH:9][C:8]=1[C:19]([F:20])([F:21])[F:22]

Participants

6

Reactant 3

HCID 122723-IodophenolHCID 516892Sodium BicarbonateHCID 16756174HCID 16756174, compound

Product 1

HCID 58674384HCID 58674384, compound

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalyst2×HCID 6342AcetonitrileSolvent

Procedure

To a flame-dried flask, NaHCO3 (5.20 g, 61.88 mmol), 3 Å molecular sieves (10.9 g), N-(4-chloro-3-(trifluoromethyl)phenyl)methacrylamide (6.51 g, 24.75 mmol), and 3-iodophenol (5.99 g, 27.23 mmol) were added under an atmosphere of argon. The solids were then dissolved in ACN (100 mL) and stirred at rt for 10 min. PPh (650 mg, 2.48 mmol) was added and argon bubbled through the reaction mixture. Pd(OAc)2 (278 mg, 1.24 mmol) was added and the reaction mixture was heated at 60° C. for 12 h. Additional palladium acetate was added and the reaction mixture was heated for 24 h. The mixture was cooled to rt and filtered through a pad of Celite. The filtrate was washed with sat. NaHCO3 and the aqueous solution extracted with EtOAc. The combined organic solutions were dried over Na2SO4, filtered, and concentrated to provide a brown oil. Purification by column chromatography (SiO2, 0-10% Et2O in DCM) provided the titled compound. LCMS, FA: Rt=1.94 min, [MH+ 356.0].

Workup

  1. additionPPh (650 mg, 2.48 mmol) was added
  2. customargon bubbled through the reaction mixture
  3. temperaturethe reaction mixture was heated at 60° C. for 12 h
  4. temperaturethe reaction mixture was heated for 24 h
  5. temperatureThe mixture was cooled to rt
  6. filtrationfiltered through a pad of Celite
  7. washThe filtrate was washed with sat. NaHCO3
  8. extractionthe aqueous solution extracted with EtOAc
  9. dry with materialThe combined organic solutions were dried over Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customto provide a brown oil
  13. customPurification by column chromatography (SiO2, 0-10% Et2O in DCM)

Sources & evidence

ORD record
ord-e202d8b7208b4d68aef7dc54a0841d79
Source dataset
uspto-grants-2010_01
Patent number
US07652041B2

Reaction notes

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