Sodium hydride → HCID 67053515, compound

HRID 885753Notes

Reaction equation

HRID 885753 reaction equation
[H-].[Na+].[Br:3][C:4]1[N:5]=[C:6]([CH:10]2[CH2:13][CH2:12][CH2:11]2)[NH:7][C:8]=1[Br:9].[CH3:14][Si:15]([CH2:18][CH2:19][O:20][CH2:21]Cl)([CH3:17])[CH3:16]>C1COCC1>[Br:9][C:8]1[N:7]=[C:6]([CH:10]2[CH2:13][CH2:12][CH2:11]2)[N:5]([CH2:21][O:20][CH2:19][CH2:18][Si:15]([CH3:17])([CH3:16])[CH3:14])[C:4]=1[Br:3]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl etherHCID 67053567HCID 67053567, compound

Product 1

HCID 67053515HCID 67053515, compoundYield 16.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

A 250 ml, round-bottom flask was purged with nitrogen and charged with NaH (95%, 0.2 g, 8.3 mmol). THF (10 mL) added, and the mixture cooled to 0° C. After 5 minutes, a solution of 4,5-dibromo-2-cyclobutyl-1H-imidazole (1.76 g, 6.29 mmol, ˜40% purity) in THF (20 mL) was added dropwise from an addition funnel over 5 minutes. The reaction was stirred at 0° C. for 35 minutes and SEMCl (1.8 mL, 10.2 mmol) was then added dropwise over 2 minutes. After 5 minutes, ice bath was removed, and the reaction stirred at room temperature for 4 hours. LCMS indicated complete reaction. The reaction was then carefully quenched with water (1.5 mL). Heptane (250 mL) was added and organic layer was washed with water (200 mL). The aqueous layer was extracted with heptane (100 mL), and the combined organic layers were washed with water and brine, dried (Na2SO4), and concentrated to give 2.14 g of crude material. The crude material was purified by flash chromatography (SiO2; EtOAc in heptane) to afford 4,5-dibromo-2-cyclobutyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazole (0.43 g) as a yellow oil: LCMS(m/z) 408.9 (MH+), tR=1.25 minutes.

Workup

  1. customA 250 ml, round-bottom flask was purged with nitrogen
  2. waitAfter 5 minutes
  3. customice bath was removed
  4. stirringthe reaction stirred at room temperature for 4 hours
  5. customreaction
  6. customThe reaction was then carefully quenched with water (1.5 mL)
  7. additionHeptane (250 mL) was added
  8. washorganic layer was washed with water (200 mL)
  9. extractionThe aqueous layer was extracted with heptane (100 mL)
  10. washthe combined organic layers were washed with water and brine
  11. dry with materialdried (Na2SO4)
  12. concentrationconcentrated
  13. customto give 2.14 g of crude material
  14. customThe crude material was purified by flash chromatography (SiO2; EtOAc in heptane)

Sources & evidence

ORD record
ord-12e8a4f54a4b4f79811d31784fff4aa0
Source dataset
uspto-grants-2012_08
Patent number
US08242260B2

Reaction notes

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