Iodine → 2-Iodo-1-[2-(trimethyl-silanyl)ethoxymethyl]-1h-benzoimidazole

HRID 1862129Notes

Reaction equation

HRID 1862129 reaction equation
[CH3:1][Si:2]([CH3:17])([CH3:16])[CH2:3][CH2:4][O:5][CH2:6][N:7]1[C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=2[N:9]=[CH:8]1.C([Li])CCC.[I:23]I>C1COCC1>[I:23][C:8]1[N:7]([CH2:6][O:5][CH2:4][CH2:3][Si:2]([CH3:17])([CH3:16])[CH3:1])[C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=2[N:9]=1

Participants

5

Reactant 3

HCID 807IodineHCID 109229071-((2-(Trimethylsilyl)ethoxy)methyl)-1H-benzo[D]imidazoleHCID 178418339Butyllithium

Product 1

HCID 218773282-Iodo-1-[2-(trimethyl-silanyl)ethoxymethyl]-1h-benzoimidazoleYield 63.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-78 °C

Procedure

A solution of 1-[2-(trimethyl-silanyl)-ethoxymethyl]-1H-benzoimidazole (5.029 g, 20.25 mmol) (see Witten et al., J. Org. Chem., 51, 1891-1894 (1986)) in THF (50 mL) was cooled to −78° C. and added dropwise over 12 min via cannula to a flask containing n-butyllithium (2.5 M in hexanes, 12.2 mL) in THF (30 mL) at −78° C. under argon. After stirring for 25 min at −78° C., the flask was warmed to 0° C. for 10 min, then cooled again to −78° C. This solution was then added via cannula to a second flask containing iodine (25.7 g, 101 mmol) in THF (50 mL) at −78° C. Once the addition was complete (˜5 min), the cooling bath was removed, and stirring was continued for 30 min. The reaction mixture was partitioned between ethyl acetate (500 mL) and water (100 mL). The organic layer was washed with saturated aqueous sodium metabisulfite (2×100 mL) to remove the dark iodine color, dried (MgSO4), and concentrated in vacuo. Purification by flash chromatography (10% to 50% ethyl acetate/hexanes) yielded 4.79 g (63%) of pure 2-iodo-1-[2-(trimethyl-silanyl)-ethoxymethyl]-1H-benzoimidazole as a yellow solid. 1H NMR (300 MHz, CDCl3) δ 7.76-7.72 (m, 1H), 7.54-7.51 (m, 1H), 7.29-7.25 (m, 2H), 5.54 (s, 2H), 3.59 (t, 2H, J=8.1 Hz), 0.92 (t, 2H, J=8.1 Hz), −0.03 (s, 9H). Anal. (C13H19IN2OS) C, H. Calculated: C, 41.71; H, 5.12; I, 33.90; N, 7.48. Found: C, 41.90; H, 5.09; I, 34.00; N, 7.37.

Workup

  1. additionadded dropwise over 12 min via cannula to a flask
  2. temperaturethe flask was warmed to 0° C. for 10 min
  3. temperaturecooled again to −78° C
  4. additionThis solution was then added via cannula to a second flask
  5. additionOnce the addition
  6. custom(˜5 min)
  7. customthe cooling bath was removed
  8. stirringstirring
  9. waitwas continued for 30 min
  10. customThe reaction mixture was partitioned between ethyl acetate (500 mL) and water (100 mL)
  11. washThe organic layer was washed with saturated aqueous sodium metabisulfite (2×100 mL)
  12. customto remove the dark iodine color
  13. dry with materialdried (MgSO4)
  14. concentrationconcentrated in vacuo
  15. customPurification by flash chromatography (10% to 50% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-12428c09bfb04869a84e0ac76b435484
Source dataset
uspto-grants-2003_03
Patent number
US06534524B1

Reaction notes

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