Sodium hydride → 2,4-dibromo-5-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-2-yl)thiazole

HRID 2282301Notes

Reaction equation

HRID 2282301 reaction equation
[H-].[Na+].[Br:3][C:4]1[S:5][C:6]([C:10]2[NH:11][CH:12]=[CH:13][N:14]=2)=[C:7]([Br:9])[N:8]=1.[CH3:15][Si:16]([CH3:23])([CH3:22])[CH2:17][CH2:18][O:19][CH2:20]Cl>C1COCC1>[Br:3][C:4]1[S:5][C:6]([C:10]2[N:14]([CH2:20][O:19][CH2:18][CH2:17][Si:16]([CH3:23])([CH3:22])[CH3:15])[CH:13]=[CH:12][N:11]=2)=[C:7]([Br:9])[N:8]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl etherHCID 580948752,4-dibromo-5-(1H-imidazol-2-yl)thiazole

Product 1

HCID 580947602,4-dibromo-5-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-2-yl)thiazoleYield 81.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a mixture of sodium hydride (2.89 g, 72.2 mmol) in THF (431 mL) was added 2,4-dibromo-5-(1H-imidazol-2-yl)thiazole (18.81 g, 60.88 mmol) in THF (60 mL) at 0° C. After stirring 30 min, [β-(Trimethylsilyl)ethoxy]methyl chloride (11.85 mL, 66.96 mmol) in THF (24 mL) was slowly added at 0° C. After 30 min at this temperature, the reaction was quenched by addition of MeOH (20 mL). The solvent was evaporated and the residue was purified by ISCO chromatography, eluted with EtOAc in hexanes, 0-25%. Product was obtained as colorless oil (21.84 g, 81.6%). LCMS: (AA) ES+, 440, 442. 1H NMR (300 MHz, d1-chloroform) δ: 7.24 (dd, 2H) 5.27 (s, 2H) 3.39 (t, 2H) 0.85 (t, 2H) −0.03 (s, 9H).

Workup

  1. waitAfter 30 min at this temperature
  2. customthe reaction was quenched by addition of MeOH (20 mL)
  3. customThe solvent was evaporated
  4. customthe residue was purified by ISCO chromatography
  5. washeluted with EtOAc in hexanes, 0-25%

Sources & evidence

ORD record
ord-4a013d121c4945ec8ecccb9623cd3159
Source dataset
uspto-grants-2015_09
Patent number
US09139589B2

Reaction notes

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