Hydrochloric Acid → 1-Fluoro-2-(4-fluoro-phenoxy)-3-Methoxy benzene

HRID 332569

Reaction equation

HRID 332569 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([O:8][CH3:9])[C:3]=1[OH:10].CN(C)CC(O)=O.Cl.C([O-])([O-])=O.[Cs+].[Cs+].[F:25][C:26]1[CH:31]=[CH:30][C:29](I)=[CH:28][CH:27]=1>O1CCOCC1.[Cu]>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([O:8][CH3:9])[C:3]=1[O:10][C:29]1[CH:30]=[CH:31][C:26]([F:25])=[CH:27][CH:28]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 673N,N-DimethylglycineHCID 96054-FluoroiodobenzeneHCID 10796Cesium carbonateHCID 27373672-Fluoro-6-methoxyphenol

Product 1

HCID 577011181-Fluoro-2-(4-fluoro-phenoxy)-3-Methoxy benzeneYield 6,350.2%

Reagents, catalysts & solvents 2

HCID 23978CopperCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
105 °C

Procedure

To a suspension of 2-fluoro-6-methoxy phenol (1) (2.8 g, 20 mmol), N,N-dimethyl glycine.HCl (837 mg, 6 mmol), Cs2CO3 (13 g, 40 mmol), 1-fluoro-4-iodobenzene (2.3 mL, 20 mmol), in Dioxane (40 ml) was added copper iodone (381 mg, 2 mmol). The reaction mixture was stirred at 105° C. over 1 week. Upon heating the reaction mixture turned from brown to a bright green. After cooling to room temperature, the reaction mixture was filtered and the filtrate was concentrated in-vacuo. The crude was purified by silica gel eluted with hexane/EtOAc (10:1), concentrated in-vacuo, to provide 300 g (21% yield) of product (2).

Workup

  1. temperatureUpon heating the reaction mixture
  2. temperatureAfter cooling to room temperature
  3. filtrationthe reaction mixture was filtered
  4. concentrationthe filtrate was concentrated in-vacuo
  5. customThe crude was purified by silica gel
  6. washeluted with hexane/EtOAc (10:1)
  7. concentrationconcentrated in-vacuo

Sources & evidence

ORD record
ord-6114c9b5157c4a06afa58a4a0bff2316
Source dataset
uspto-grants-2014_11
Patent number
US08877816B2

Linked notes

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