Water → 4,5-dibromo-2-tert-butyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazole

HRID 885747Notes

Reaction equation

HRID 885747 reaction equation
[C:1]([C:5]1[NH:6][C:7]([Br:11])=[C:8]([Br:10])[N:9]=1)([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[CH3:14][Si:15]([CH2:18][CH2:19][O:20][CH2:21]Cl)([CH3:17])[CH3:16].O>C1COCC1.CCOC(C)=O>[Br:11][C:7]1[N:6]=[C:5]([C:1]([CH3:4])([CH3:2])[CH3:3])[N:9]([CH2:21][O:20][CH2:19][CH2:18][Si:15]([CH3:17])([CH3:16])[CH3:14])[C:8]=1[Br:10]

Participants

7

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl etherHCID 665906694,5-dibromo-2-tert-butyl-1H-imidazole

Product 1

HCID 665910814,5-dibromo-2-tert-butyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazoleYield 101.9%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a cooled solution of 2-t-butyl-4,5-dibromoimidazole (1.4 grams, 5.0 mmol; Example 5, Step 2) in dry THF (10 mL) at 0° C. was added sodium hydride (95%, 0.15 grams, 6.0 mmol) portion wise. The reaction mixture was stirred for 10 minutes at 0° C., at room temperature for 40 minutes. The reaction was re-cooled to 0° C. and SEM-chloride (0.97 ml, 5.5 mmol) was added in dropwise. The reaction mixture was stirred overnight allowing the ice bath to expire and poured into a mixture of water (30 mL) and EtOAc (50 mL). The resulting layers were partitioned and separated. The organic portion was washed with brine, then water, dried (Na2SO4), and concentrated. The remaining residue was purified by flash chromatography (SiO2, 0-10% EtOAc in hexanes) to provide 2.1 g of 4,5-dibromo-2-tert-butyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazole: LCMS(m/z): 412.9 (MH+), tR=1.320 minutes; 1H NMR (400 MHz, CDCl3) δ 8.75 (dd, 1H,), 7.92 (dd, 1H,), 5.90 (s, 2H), 3.51 (m, 2H), 1.55 (s, 9H), 0.82 (m, 2H), 0.08 (s, 9H).

Workup

  1. temperatureThe reaction was re-cooled to 0° C.
  2. stirringThe reaction mixture was stirred overnight
  3. customThe resulting layers were partitioned
  4. customseparated
  5. washThe organic portion was washed with brine
  6. dry with materialwater, dried (Na2SO4)
  7. concentrationconcentrated
  8. customThe remaining residue was purified by flash chromatography (SiO2, 0-10% EtOAc in hexanes)

Sources & evidence

ORD record
ord-8881fef6badf462e95e115f7d4dd8edb
Source dataset
uspto-grants-2012_08
Patent number
US08242260B2

Reaction notes

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