Sodium hydride → HCID 67053538, compound

HRID 535740Notes

Reaction equation

HRID 535740 reaction equation
[Br:1][C:2]1[N:3]=[C:4]([CH:8]2[CH2:10][CH2:9]2)[NH:5][C:6]=1[Br:7].[H-].[Na+].[CH3:13][Si:14]([CH3:21])([CH3:20])[CH2:15][CH2:16][O:17][CH2:18]Cl>C1COCC1>[Br:1][C:2]1[N:3]=[C:4]([CH:8]2[CH2:10][CH2:9]2)[N:5]([CH2:18][O:17][CH2:16][CH2:15][Si:14]([CH3:21])([CH3:20])[CH3:13])[C:6]=1[Br:7]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl etherHCID 67053548HCID 67053548, compound

Product 1

HCID 67053538HCID 67053538, compoundYield 88.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 4,5-dibromo-2-cyclopropyl-1H-imidazole (60 g, 226 mmol) in THF (150 mL) was added dropwise over 50 minutes under nitrogen to a stirring mixture of sodium hydride (95%, 6.3 g, 250 mmol) in dry THF (150 mL) at 0° C. The reaction mixture was stirred 30 minutes and 2-(trimethylsilyl)ethoxymethylchloride (SEMCl, 40 mL, 38 g, 226 mmol) was added dropwise over 50 minutes at 0° C. After stirring for 1 hour, the reaction was slowly quenched with water (20 mL) and added EtOAc (500 mL). The mixture was washed with water (2×750 mL) and the combined aqueous portions were back extracted with EtOAc (200 mL). The combined organic portions were washed with brine (1 L), dried (Na2SO4), and concentrated. The resulting residue was dissolved in heptane (200 mL) and the resulting solution was passed through a pad of silica gel, eluting with heptane (4×500 mL) and EtOAc-heptane (1:4, 2×250 mL) to give 4,5-dibromo-2-cyclopropyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazole (79 g, 199 mmol, 88%) as a pale yellow solid after concentration: LCMS (m/z) 394.9 (MH+), tR=1.20 minutes, 1H NMR (400 MHz, CDCl3) δ ppm −0.04-0.05 (m, 9H), 0.87-1.12 (m, 6H), 1.88-2.04 (m, 1H), 3.55-3.66 (m, 2H), 5.37 (s, 2H).

Workup

  1. stirringAfter stirring for 1 hour
  2. customthe reaction was slowly quenched with water (20 mL)
  3. additionadded EtOAc (500 mL)
  4. washThe mixture was washed with water (2×750 mL)
  5. extractionthe combined aqueous portions were back extracted with EtOAc (200 mL)
  6. washThe combined organic portions were washed with brine (1 L)
  7. dry with materialdried (Na2SO4)
  8. concentrationconcentrated
  9. dissolutionThe resulting residue was dissolved in heptane (200 mL)
  10. washeluting with heptane (4×500 mL) and EtOAc-heptane (1:4, 2×250 mL)

Sources & evidence

ORD record
ord-b9b7410899bd4dea97ad895b90204066
Source dataset
uspto-grants-2014_10
Patent number
US08859548B2

Reaction notes

Loading…