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

HRID 1488088ノート

反応式

HRID 1488088 の反応式
[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

参加物

5

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

反応条件

温度
-60 °C

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-14ff84592a2f423d816dce6da5088295
出典データセット
uspto-grants-2016_08
特許番号
US09428502B2

反応ノート

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