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

HRID 2402051Notes

Reaction equation

HRID 2402051 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 81.6%

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 (18.8 g, 60.9 mmol) in THF (60 mL) at 0° C. After stirring 30 min, 2-(trimethylsilyl)ethoxymethyl chloride (11.8 mL, 66.9 mmol) in THF (24 mL) was slowly added at 0° C. After 30 min at this temperature, the reaction was quenched by the addition of MeOH (20 mL). The solvent was evaporated and the residue was purified by column chromatography on silica gel (0 to 25% EtOAc in hexanes). Product was obtained as colorless oil (21.8 g, 81.6%). LCMS: (AA) ES+, 440, 442. 1H NMR (300 MHz, CDCl3) 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 the addition of MeOH (20 mL)
  3. customThe solvent was evaporated
  4. customthe residue was purified by column chromatography on silica gel (0 to 25% EtOAc in hexanes)

Sources & evidence

ORD record
ord-42dc0525de8244698951ccba3689622d
Source dataset
uspto-grants-2014_08
Patent number
US08796271B2

Reaction notes

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