Sodium Iodide → 4-(Benzyloxy)-2-fluoro-1-iodobenzene

HRID 707498Notes

Reaction equation

HRID 707498 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12](Br)=[C:11]([F:16])[CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O1CCOCC1.[I-:23].[Na+].CNCCNC>[Cu](I)I.C(OCC)(=O)C.O>[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([I:23])=[C:11]([F:16])[CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

8

Reactant 4

HCID 5238Sodium IodideHCID 8070N,N'-DimethylethylenediamineHCID 312751,4-DioxaneHCID 222739334-(Benzyloxy)-1-bromo-2-fluorobenzene

Product 1

HCID 1181623954-(Benzyloxy)-2-fluoro-1-iodobenzeneYield 89.4%

Reagents, catalysts & solvents 3

HCID 83717Copper iodideCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

To a mixed solution of 4-(benzyloxy)-1-bromo-2-fluorobenzene (187 g, 665 mmol) described in Production Example 1-2-4 and 1,4-dioxane (300 mL) were added copper iodide (I) (12.6 g, 66.1 mmol), sodium iodide (200 g, 1.33 mol) and N,N′-dimethylethylenediamine (14.0 mL, 132 mmol) at room temperature, and the resultant mixture was stirred under a nitrogen atmosphere at 110 to 115° C. for 19 hours. The reaction mixture was cooled to room temperature, then water and ethyl acetate were added to the reaction mixture, the resultant mixture was filtrated using Celite, and a filtrate was partitioned between aqueous layer and organic layer. The aqueous layer was extracted with ethyl acetate. The combined organic layers were filtrated using a glass filter having silica gel laid thereon. The silica gel was washed with ethyl acetate, organic layers obtained were combined, and the solvent was evaporated under a reduced pressure. The resultant residue was purified by silica gel column chromatography (heptane:ethyl acetate=7:1 and then 4:1) to give the title compound (195 g, yield: 89%).

Workup

  1. filtrationthe resultant mixture was filtrated
  2. customa filtrate was partitioned between aqueous layer and organic layer
  3. extractionThe aqueous layer was extracted with ethyl acetate
  4. filtrationThe combined organic layers were filtrated
  5. filtrationfilter
  6. washThe silica gel was washed with ethyl acetate, organic layers
  7. customobtained
  8. customthe solvent was evaporated under a reduced pressure
  9. customThe resultant residue was purified by silica gel column chromatography (heptane

Sources & evidence

ORD record
ord-c93a2aa26c444a06bc299c4ef183aacd
Source dataset
uspto-grants-2015_11
Patent number
US09174998B2

Reaction notes

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