Iodine → 3'-Chloro-3-fluoro-4-iodo-5-methoxy-1,1'-biphenyl

HRID 1504471Notes

Reaction equation

HRID 1504471 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:13]=[C:12]([O:14][CH3:15])[CH:11]=[C:10]([F:16])[CH:9]=2)[CH:5]=[CH:6][CH:7]=1.C([Li])CCC.[I:22]I>C1COCC1.S([O-])([O-])(=O)=S.[Na+].[Na+].O>[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:13]=[C:12]([O:14][CH3:15])[C:11]([I:22])=[C:10]([F:16])[CH:9]=2)[CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 3

HCID 807IodineHCID 1177372123'-Chloro-3-fluoro-5-methoxy-1,1'-biphenylHCID 178418339Butyllithium

Product 1

HCID 1177370223'-Chloro-3-fluoro-4-iodo-5-methoxy-1,1'-biphenylYield 78%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×HCID 24477Sodium ThiosulfateSolvent

Procedure

A RBF was charged with 3′-chloro-3-fluoro-5-methoxy-1,1′-biphenyl (577.6 mg, 2.441 mmol) and THF (8135 μl) to give a clear solution. The flask was cooled in a dry ice-acetone bath for 10 min, then n-butyllithium (1.8M in hexanes) (1627 μl, 2.93 mmol) was added dropwise. After 30 min, a solution of iodine (929 mg, 3.66 mmol) in THF (3 mL) was added dropwise. TLC after 5 min showed conversion to a slightly lower spot. The mixture was diluted with saturated aq. sodium thiosulfate solution and warmed to room temperature. The mixture was diluted with water and extracted with EtOAc (2×), and the combined organic extracts were dried over sodium sulfate, filtered, and concentrated. The residue was purified by chromatography on silica gel (25-g Ultra SNAP column, 0-5% EtOAc/Heptane) to give 3′-chloro-3-fluoro-4-iodo-5-methoxy-1,1′-biphenyl (687 mg, 1.895 mmol, 78% yield) as an off-white solid. 1 H NMR (400 MHz, DMSO-d6) □=7.87 (td, J=1.0, 1.8 Hz, 1 H), 7.74 (td, J=1.8, 7.0 Hz, 1 H), 7.55-7.43 (m, 2 H), 7.25 (dd, J=1.8, 9.1 Hz, 1 H), 7.14-7.07 (m, 1 H), 3.97 (s, 3 H).

Workup

  1. customto give a clear solution
  2. temperatureThe flask was cooled in a dry ice-acetone bath for 10 min
  3. waitTLC after 5 min showed
  4. extractionextracted with EtOAc (2×)
  5. dry with materialthe combined organic extracts were dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by chromatography on silica gel (25-g Ultra SNAP column, 0-5% EtOAc/Heptane)

Sources & evidence

ORD record
ord-4487331214ba404c9b0b10111cfd21f7
Source dataset
uspto-grants-2015_12
Patent number
US09212182B2

Reaction notes

Loading…