Tetrahydro-4H-pyran-4-one → 4-(4-(Trifluoromethyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-2-yl)tetrahydro-2H-pyran-4-ol

HRID 1488088Notes

Reaction equation

HRID 1488088 reaction equation
[F:1][C:2]([F:17])([F:16])[C:3]1[N:4]=[CH:5][N:6]([CH2:8][O:9][CH2:10][CH2:11][Si:12]([CH3:15])([CH3:14])[CH3:13])[CH:7]=1.C([Li])CCC.[O:23]1[CH2:28][CH2:27][C:26](=[O:29])[CH2:25][CH2:24]1>O1CCCC1>[F:17][C:2]([F:16])([F:1])[C:3]1[N:4]=[C:5]([C:26]2([OH:29])[CH2:27][CH2:28][O:23][CH2:24][CH2:25]2)[N:6]([CH2:8][O:9][CH2:10][CH2:11][Si:12]([CH3:13])([CH3:14])[CH3:15])[CH:7]=1

Participants

5

Reactant 3

HCID 121599Tetrahydro-4H-pyran-4-oneHCID 136002324-trifluoromethyl-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazole2×HCID 178418339Butyllithium

Product 1

HCID 900667314-(4-(Trifluoromethyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-2-yl)tetrahydro-2H-pyran-4-olYield 87.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-60 °C

Procedure

Into a 100-mL three neck round-bottom flask, which was purged and maintained with an inert atmosphere of nitrogen, was placed a solution of 4-(trifluoromethyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazole (compound 216.2, 5 g, 18.77 mmol) in tetrahydrofuran (50 mL). This was followed by the addition of n-butyllithium (9 mL, 22.5 mmol, 2.5N in hexane) dropwise at −78° C. and stirred for 1 h at -60° C. To this was added dihydro-2H-pyran-4(3H)-one (6 g, 59.93 mmol). The resulting solution was stirred for 4 h at 0° C. in an ice/salt bath, then quenched with 10 mL of water. The resulting solution was diluted with 100 mL of NH4Cl (sat.). The aqueous phase was extracted with 2×100 mL of ethyl acetate. The combined organic layers were dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography with ethyl acetate/petroleum ether (1:4) as eluent to furnish 6 g (87%) of the title compound as a light yellow oil.

Workup

  1. customInto a 100-mL three neck round-bottom flask, which was purged
  2. temperaturemaintained with an inert atmosphere of nitrogen
  3. stirringThe resulting solution was stirred for 4 h at 0° C. in an ice/salt bath
  4. customquenched with 10 mL of water
  5. additionThe resulting solution was diluted with 100 mL of NH4Cl (sat.)
  6. extractionThe aqueous phase was extracted with 2×100 mL of ethyl acetate
  7. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by silica gel chromatography with ethyl acetate/petroleum ether (1:4) as eluent

Sources & evidence

ORD record
ord-14ff84592a2f423d816dce6da5088295
Source dataset
uspto-grants-2016_08
Patent number
US09428502B2

Reaction notes

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