Sodium hydride → HCID 69812840, compound

HRID 535753Notes

Reaction equation

HRID 535753 reaction equation
[H-].[Na+].[Br:3][C:4]1[N:5]=[C:6]([C:10]2([CH3:13])[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]([C:10]2([CH3:13])[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 hydride2×HCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl ether2×HCID 67053523HCID 67053523, compound

Product 1

HCID 69812840HCID 69812840, compoundYield 78.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

A 250 mL round-bottom flask was purged with N2 and charged with NaH (95%, 0.33 g, 13.1 mmol). THF (15 mL) added, and the mixture cooled to 0° C. After 5 minutes, a solution of 4,5-dibromo-2-(1-methylcyclopropyl)-1H-imidazole (3.0 g, 10.7 mmol) in THF (20 mL) was added dropwise from an addition funnel over 5 minutes. The light tan solution was stirred at 0° C. for 25 minutes and SEMCl (2.1 mL, 11.8 mmol) was then added dropwise over 2 minutes. After 5 minutes, ice bath was removed, and the reaction stirred at room temperature. After stirring 2 hours, LCMS indicated 90% conversion. Another 0.3 mL of SEMCl (0.3 mL, 1.7 mmol) was added. LCMS indicates that the reaction has not proceeded; additional NaH (95%, 51 mg, 2.0 mmol) was added with concomitant gas evolution. After 15 minutes, LCMS indicated complete reaction. The reaction was quenched with water (1 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 4.46 g of crude material. The crude material was purified by flash chromatography (SiO2; 0-25% EtOAc in heptane) to give the product (3.45 g) as a light yellow oil: LCMS (m/z) 409.0 (MH+), tR=1.27 minutes.

Workup

  1. customA 250 mL round-bottom flask was purged with N2
  2. waitAfter 5 minutes
  3. customice bath was removed
  4. stirringthe reaction stirred at room temperature
  5. stirringAfter stirring 2 hours
  6. waitAfter 15 minutes
  7. customreaction
  8. customThe reaction was quenched with water (1 mL)
  9. additionHeptane (250 mL) was added
  10. washorganic layer was washed with water (200 mL)
  11. extractionThe aqueous layer was extracted with heptane (100 mL)
  12. washthe combined organic layers were washed with water and brine
  13. dry with materialdried (Na2SO4)
  14. concentrationconcentrated
  15. customto give 4.46 g of crude material
  16. customThe crude material was purified by flash chromatography (SiO2; 0-25% EtOAc in heptane)

Sources & evidence

ORD record
ord-82b9849169334feaa0984e53274ceb2a
Source dataset
uspto-grants-2014_10
Patent number
US08859548B2

Reaction notes

Loading…