Acetic Acid → 2-Chloro-3'-fluoro-4-iodo-5-methoxy-1,1'-biphenyl

HRID 1473540Notes

Reaction equation

HRID 1473540 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[CH:4][C:3]=1[C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([F:16])[CH:11]=1.CC(O)=O.S(=O)(=O)(O)O.C1C(=O)N([I:33])C(=O)C1>C(Cl)Cl>[Cl:1][C:2]1[CH:7]=[C:6]([I:33])[C:5]([O:8][CH3:9])=[CH:4][C:3]=1[C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([F:16])[CH:11]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 1118Sulfuric AcidHCID 120273N-IodosuccinimideHCID 866875982-Chloro-3'-fluoro-5-methoxy-1,1'-biphenyl

Product 1

HCID 866876002-Chloro-3'-fluoro-4-iodo-5-methoxy-1,1'-biphenylYield 85.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A round-bottom flask was charged with 2-chloro-3′-fluoro-5-methoxy-1,1′-biphenyl (1.288 g, 5.44 mmol), DCM (8.00 ml), AcOH (8.00 ml), and sulfuric acid (0.160 ml, 2.99 mmol) to give a clear solution. n-Iodosuccinimide (1.224 g, 5.44 mmol) was added in one portion to give a maroon-colored solution. After 7 h, the mixture was diluted with DCM, washed with water, washed with saturated aq. sodium thiosulfate, dried over sodium sulfate, filtered, and concentrated. The residue was purified by chromatography on silica gel (40-g Redi-Sep Gold column, 25-g silica gel column, 0-5% EtOAc/Heptane) give 2-chloro-3′-fluoro-4-iodo-5-methoxy-1,1′-biphenyl (1.68 g, 4.63 mmol, 85% yield) as a clear oil. m/z (ESI) 362.0 (M+H)+.

Workup

  1. customto give a clear solution
  2. customto give a maroon-colored solution
  3. washwashed with water
  4. washwashed with saturated aq. sodium thiosulfate
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by chromatography on silica gel (40-g Redi-Sep Gold column, 25-g silica gel column, 0-5% EtOAc/Heptane)

Sources & evidence

ORD record
ord-1cbd104094a04177ab5b95ed1858d325
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

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