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

HRID 535750Notes

Reaction equation

HRID 535750 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-59712ab3775d434fbfbf01c40a424b05
Source dataset
uspto-grants-2014_10
Patent number
US08859548B2

Reaction notes

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