Methyl iodide → 2-(4-Methoxytetrahydro-2H-pyran-4-yl)-4-(trifluoromethyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazole

HRID 1488089Notes

Reaction equation

HRID 1488089 reaction equation
[F:1][C:2]([F:24])([F:23])[C:3]1[N:4]=[C:5]([C:16]2([OH:22])[CH2:21][CH2:20][O:19][CH2:18][CH2:17]2)[N:6]([CH2:8][O:9][CH2:10][CH2:11][Si:12]([CH3:15])([CH3:14])[CH3:13])[CH:7]=1.[H-].[Na+].[CH3:27]I>O1CCCC1>[CH3:27][O:22][C:16]1([C:5]2[N:6]([CH2:8][O:9][CH2:10][CH2:11][Si:12]([CH3:15])([CH3:13])[CH3:14])[CH:7]=[C:3]([C:2]([F:1])([F:23])[F:24])[N:4]=2)[CH2:17][CH2:18][O:19][CH2:20][CH2:21]1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 900667314-(4-(Trifluoromethyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-2-yl)tetrahydro-2H-pyran-4-ol2×

Product 1

HCID 900307462-(4-Methoxytetrahydro-2H-pyran-4-yl)-4-(trifluoromethyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazoleYield 77%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Into a 250-mL three neck round-bottom flask, which was purged and maintained with an inert atmosphere of nitrogen, was placed a solution of 4-(4-(trifluoromethyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-2-yl)tetrahydro-2H-pyran-4-ol (compound 216.3, 2 g, 5.46 mmol) in tetrahydrofuran (100 mL). This was followed by the addition of sodium hydride (262 mg, 6.55 mmol, 60%) at −70° C. and stirred for 30 min. To this was added MeI (930 mg, 6.55 mmol). The resulting solution was stirred for 1 h at room temperature, then carefully quenched with 10 mL of water. The resulting mixture was diluted with 50 mL of brine. The aqueous phase was extracted with 2×50 mL of ethyl acetate. The combined organic layers were washed with 1×50 mL of brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography with ethyl acetate/petroleum ether (1:3) as eluent to furnish 1.6 g (77%) of the title compound as light brown oil.

Workup

  1. customInto a 250-mL three neck round-bottom flask, which was purged
  2. temperaturemaintained with an inert atmosphere of nitrogen
  3. stirringThe resulting solution was stirred for 1 h at room temperature
  4. customcarefully quenched with 10 mL of water
  5. additionThe resulting mixture was diluted with 50 mL of brine
  6. extractionThe aqueous phase was extracted with 2×50 mL of ethyl acetate
  7. washThe combined organic layers were washed with 1×50 mL of brine
  8. dry with materialdried over anhydrous sodium sulfate
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was purified by silica gel chromatography with ethyl acetate/petroleum ether (1:3) as eluent

Sources & evidence

ORD record
ord-5b611557a83a48d08975631f57228dcd
Source dataset
uspto-grants-2016_08
Patent number
US09428502B2

Reaction notes

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