Acetic Acid → 1-Chloro-2-fluoro-4-iodo-5-methoxybenzene

HRID 1473574

Reaction equation

HRID 1473574 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([O:8][CH3:9])[CH:5]=[CH:4][C:3]=1[F:10].CC(O)=O.S(=O)(=O)(O)O.C1C(=O)N([I:27])C(=O)C1>C(Cl)Cl>[Cl:1][C:2]1[CH:7]=[C:6]([O:8][CH3:9])[C:5]([I:27])=[CH:4][C:3]=1[F:10]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 1118Sulfuric AcidHCID 120273N-IodosuccinimideHCID 27735853-Chloro-4-fluoroanisole

Product 1

HCID 210706301-Chloro-2-fluoro-4-iodo-5-methoxybenzeneYield 70.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A round-bottom flask was charged with 2-chloro-1-fluoro-4-methoxybenzene (Alfa Aesar, Ward Hill, Mass., 2.714 g, 16.90 mmol), DCM (24.86 ml), AcOH (24.86 ml), and sulfuric acid (0.496 ml, 9.30 mmol) to give a solution. n-iodosuccinimide (3.80 g, 16.90 mmol) was added in a single portion. TLC showed what appeared to be conversion of the starting material to a slightly higher, move UV-active spot. The mixture was diluted with DCM, washed with water (2×), washed with saturated aq. sodium thiosulfate, dried over sodium sulfate, filtered, and concentrated. The residue was purified by chromatography on silica gel (50-g SNAP Ultra column, 0-10% EtOAc/Heptane) to give 3.409 g of a clear oil. This oil was used directly in the next reaction without further purification.

Workup

  1. customto give a solution
  2. washwashed with water (2×)
  3. washwashed with saturated aq. sodium thiosulfate
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by chromatography on silica gel (50-g SNAP Ultra column, 0-10% EtOAc/Heptane)

Sources & evidence

ORD record
ord-0323f11afe314e979ec1f231d4171d33
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Linked notes

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