Sodium hydride → HCID 18446904, compound

HRID 538401Notes

Reaction equation

HRID 538401 reaction equation
[H-].[Na+].[C:3]1([C:9]2[NH:10][CH:11]=[C:12]([C:14]3[CH:19]=[CH:18][N:17]=[CH:16][CH:15]=3)[N:13]=2)[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[CH3:20][Si:21]([CH3:28])([CH3:27])[CH2:22][CH2:23][O:24][CH2:25]Cl>CN(C=O)C>[C:3]1([C:9]2[N:10]([CH2:25][O:24][CH2:23][CH2:22][Si:21]([CH3:28])([CH3:27])[CH3:20])[CH:11]=[C:12]([C:14]3[CH:15]=[CH:16][N:17]=[CH:18][CH:19]=3)[N:13]=2)[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl etherHCID 178420139HCID 178420139, compound

Product 1

HCID 18446904HCID 18446904, compoundYield 75.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

60% Sodium hydride (200 mg, 5.0 mmol) was added slowly into a solution of 4-(2-phenyl-1H-imidazol-4-yl)pyridine (1.0 g, 4.5 mmol; Example 1, Step 1) in dry DMF (5 mL) at 0° C. The reaction mixture was stirred at rt for 1 h and re-cooled to 0° C. and 2-(trimethylsilyl)ethoxymethyl chloride (SEM chloride; 0.88 mL, 0.83 g, 5.0 mmol) was added. The reaction was stirred at 10° C. for 2 h and quenched with water (40 mL). The mixture was partitioned and extracted with EtOAc (3×60 mL) and the organic layers were combined, dried (Na2SO4), and concentrated. The resulting residue was purified by flash chromatography (SiO2, 100:0-90:10 DCM-MeOH) to give 1.2 g (75%) of 4-(2-phenyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-4-yl)pyridine: 1H NMR (CDCl3) δ 8.61 (d, J=6.0, 1.2 Hz, 2H), 7.81 (d, J=8.0, 1.6 Hz, 2H), 7.74 (d, J=6.0, 1.2 Hz, 2H), 7.58 (s, 1H), 7.49 (m, 3H), 5.30 (s, 2H), 3.60 (t, J=8.0 Hz, 2H), 0.94 (t, J=8.0 Hz, 2H), 0.00 (s, 9H).

Workup

  1. temperaturere-cooled to 0° C.
  2. stirringThe reaction was stirred at 10° C. for 2 h
  3. customquenched with water (40 mL)
  4. customThe mixture was partitioned
  5. extractionextracted with EtOAc (3×60 mL)
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated
  8. customThe resulting residue was purified by flash chromatography (SiO2, 100:0-90:10 DCM-MeOH)

Sources & evidence

ORD record
ord-6f5dc00948034e06aa922bc0a93b2e33
Source dataset
uspto-grants-2014_10
Patent number
US08865732B2

Reaction notes

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