Water → 2-[5-(Toluene-4-sulfonyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazol-4-yl]-pyridine

HRID 352150Notes

Reaction equation

HRID 352150 reaction equation
[C:1]1([CH3:21])[CH:6]=[CH:5][C:4]([S:7]([C:10]2[NH:14][CH:13]=[N:12][C:11]=2[C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][N:16]=2)(=[O:9])=[O:8])=[CH:3][CH:2]=1.[H-].[Na+].[CH3:24][Si:25]([CH2:28][CH2:29][O:30][CH2:31]Cl)([CH3:27])[CH3:26].O>CN(C=O)C>[C:1]1([CH3:21])[CH:2]=[CH:3][C:4]([S:7]([C:10]2[N:14]([CH2:31][O:30][CH2:29][CH2:28][Si:25]([CH3:27])([CH3:26])[CH3:24])[CH:13]=[N:12][C:11]=2[C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][N:16]=2)(=[O:9])=[O:8])=[CH:5][CH:6]=1

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl etherHCID 121468662-[5-(Toluene-4-sulfonyl)-1H-imidazol-4-yl]-pyridine

Product 1

HCID 121468712-[5-(Toluene-4-sulfonyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazol-4-yl]-pyridine

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of 2-[5-(Toluene-4-sulfonyl)-1H-imidazol-4-yl]-pyridine (Tetrahedron Lett. 1976, 285) (1.65 g, 5.51 mmol) in dry DMF (15 mL) was added NaH (60% in mineral oil, 0.36 g, 9.0 mmol) at room temperature under N2. After 30 minutes stirring, SEM-Cl (1.21 mL, 6.83 mmol) was added through a syringe. The slurry was further stirred at room temperature for 6 hours, and then poured into cold H2O (100 mL), extracted with dichloromethane (3×50 mL). Combined dichloromethane solution was washed with H2O (2×50 mL) and brine (50 mL). Flash silica gel chromatography (hexane to 2:1 hexane/ethyl acetate) afforded the 2-[5-(Toluene-4-sulfonyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazol-4-yl]-pyridine as a syrup intermediate in the forms of 1:1 regioisomers (1.89 g, 80%). 1H NMR δ−0.09 (s, 9H), 0.75 (t, 2H, J=7), 2.38 (s, 3H), 3.30 (t, 2H, J=7), 5.40 (s, 2H), 7.22 (d, 2H, J=8), 7.4 (t, 1H, J=6), 7.65-7.95 (m, 5 H), 8.70 (d, 1H, J=4) ppm; the other regio-isomer shows chemical shift at δ−0.02 (s, 9H), 0.8 (t, 2H, J=7), 2.41 (s, 3H), 3.41(t, 2H, J=7), 5.65 (s, 2H), 7.2-7.35 (m, 2H), 7.70-7.90 (m, 5H), 8.1 (d, 1H, J=8), 8.68 (d, 1H, J=4)ppm; (ESMS calcd for (C21H27N3O3SSi): 429.2; found: 430.4 (M+H)+.

Workup

  1. stirringThe slurry was further stirred at room temperature for 6 hours
  2. extractionextracted with dichloromethane (3×50 mL)
  3. washCombined dichloromethane solution was washed with H2O (2×50 mL) and brine (50 mL)

Sources & evidence

ORD record
ord-826792e0d39b457183b8c2cb394e5d86
Source dataset
uspto-grants-2004_06
Patent number
US06743919B2

Reaction notes

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