Sodium hydride → 1-Bromo-4-[[(4-iodophenyl)methoxy]methyl]benzene

HRID 716670Notes

Reaction equation

HRID 716670 reaction equation
[I:1][C:2]1[CH:9]=[CH:8][C:5]([CH2:6][OH:7])=[CH:4][CH:3]=1.[H-].[Na+].[Br:12][C:13]1[CH:20]=[CH:19][C:16]([CH2:17]Br)=[CH:15][CH:14]=1>CN(C=O)C.[I-].C([N+](CCCC)(CCCC)CCCC)CCC>[Br:12][C:13]1[CH:20]=[CH:19][C:16]([CH2:17][O:7][CH2:6][C:5]2[CH:8]=[CH:9][C:2]([I:1])=[CH:3][CH:4]=2)=[CH:15][CH:14]=1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 290124-Iodobenzyl alcoholHCID 685274-Bromobenzyl bromide

Product 1

HCID 667643561-Bromo-4-[[(4-iodophenyl)methoxy]methyl]benzeneYield 51%

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 6228DimethylformamideSolvent

Procedure

1-Bromo-4-[(4-iodobenzyloxy)methyl]benzene (3v) was prepared using an non-optimized procedure as follows. To a stirred solution of 4-iodobenzyl alcohol (1.33 g, 5.5 mmol, 1.1 equiv) in DMF (40 mL) at 0° C. was added NaH (240 mg, 60% in mineral oil, 6.0 mmol, 1.2 equiv), and the mixture was warmed to room temperature and stirred for 30 min. The mixture was cooled to 0° C., and 4-bromobenzyl bromide (1.25 g, 5.0 mmol, 1.0 equiv) and tetra-n-butylammonium iodide (92.3 mg, 0.25 mmol, 0.050 equiv) were added. The reaction mixture was warmed to room temperature, stirred for 2 h and quenched with saturated aqueous NH4Cl solution. The mixture was extracted with Et2O, and the organic layer was washed with 1 M aqueous HCl solution and brine and dried over Na2SO4. After evaporation of the solvent, the crude mixture was purified by flash silica gel column chromatography (hexane/Et2O=400/1 to 20/1) to give 1-bromo-4-[(4-iodobenzyloxy)methyl]benzene (3v) as a white solid (1.02 g, 51% yield). 1H NMR (400 MHz, CDCl3): δ 7.68 (d, J=8.4 Hz, 2 H), 7.48 (d, J=8.4 Hz, 2 H), 7.22 (d, J=8.4 Hz, 2 H), 7.10 (d, J=8.4 Hz, 2 H), 4.49 (s, 4 H). 13C{1H} NMR (125 MHz, CDCl3): δ 137.9, 137.8, 137.2, 131.8, 129.8, 129.6, 121.9, 93.4, 71.8, 71.7. Anal. calcd. for C14H12BrIO: C, 41.72; H, 3.00; found: C, 41.71; H, 2.77.

Workup

  1. custom1-Bromo-4-[(4-iodobenzyloxy)methyl]benzene (3v) was prepared
  2. temperatureThe mixture was cooled to 0° C.
  3. temperatureThe reaction mixture was warmed to room temperature
  4. stirringstirred for 2 h
  5. customquenched with saturated aqueous NH4Cl solution
  6. extractionThe mixture was extracted with Et2O
  7. washthe organic layer was washed with 1 M aqueous HCl solution and brine
  8. dry with materialdried over Na2SO4
  9. customAfter evaporation of the solvent
  10. customthe crude mixture was purified by flash silica gel column chromatography (hexane/Et2O=400/1 to 20/1)

Sources & evidence

ORD record
ord-19097de63d034118be0b639cf656ad91
Source dataset
uspto-grants-2015_11
Patent number
US09193648B2

Reaction notes

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