2,2,2-Trifluoroethyl trifluoromethanesulfonate → 5-(2,3-Difluorophenyl)-1-(2,2,2-trifluoroethyl)piperidin-2-one

HRID 406560ノート

反応式

HRID 406560 の反応式
[F:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[CH:4][C:3]=1[CH:9]1[CH2:14][NH:13][C:12](=[O:15])[CH2:11][CH2:10]1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].O([CH2:34][C:35]([F:38])([F:37])[F:36])S(C(F)(F)F)(=O)=O>C1COCC1.CN1C(=O)CCC1>[F:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[CH:4][C:3]=1[CH:9]1[CH2:14][N:13]([CH2:34][C:35]([F:38])([F:37])[F:36])[C:12](=[O:15])[CH2:11][CH2:10]1

参加物

6

反応物 3

HCID 803662,2,2-Trifluoroethyl trifluoromethanesulfonateHCID 2733832Lithium HexamethyldisilazideHCID 687484265-(2,3-Difluorophenyl)piperidin-2-one

生成物 1

HCID 687471945-(2,3-Difluorophenyl)-1-(2,2,2-trifluoroethyl)piperidin-2-one

試薬・触媒・溶媒 2

HCID 8028Tetrahydrofuran溶媒HCID 13387N-methyl-2-pyrrolidone溶媒

反応条件

温度
0 °C

実験手順

To a stirred solution of 5-(2,3-difluorophenyl)piperidin-2-one (8.88 g, 42 mmol) in THF (250 mL) and NMP (170 mL) at 0° C. was added lithium bis(trimethylsilyl)amide (1.0 M in THF, 48 mL, 48 mmol) over 5 min, keeping the internal temperature of the reaction mixture below 5° C. The resulting mixture was stirred at 0° C. for 15 min, then 2,2,2-trifluoroethyl triflate (11.2 g, 48 mmol) was added dropwise, keeping the internal temperature of the reaction mixture below 5° C. The reaction mixture was allowed to warm slowly to ambient temperature and stirring was continued for 3 h. The resulting mixture was partitioned between saturated aqueous sodium bicarbonate (800 mL) and EtOAc (1 L). The organic layer was removed and the aqueous phase was extracted further with EtOAc (500 mL). The combined organic extracts were washed with water, then brine, then dried over sodium sulfate, filtered, and concentrated to dryness in vacuo. The crude product was purified by silica gel chromatography, eluting with a gradient of hexanes:EtOAc—100:0 to 0:100, to give the title compound. MS: m/z=293.9 (M+1).

後処理

  1. customthe internal temperature of the reaction mixture below 5° C
  2. customthe internal temperature of the reaction mixture below 5° C
  3. temperatureto warm slowly to ambient temperature
  4. stirringstirring
  5. waitwas continued for 3 h
  6. customThe resulting mixture was partitioned between saturated aqueous sodium bicarbonate (800 mL) and EtOAc (1 L)
  7. customThe organic layer was removed
  8. extractionthe aqueous phase was extracted further with EtOAc (500 mL)
  9. washThe combined organic extracts were washed with water
  10. dry with materialbrine, then dried over sodium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated to dryness in vacuo
  13. customThe crude product was purified by silica gel chromatography
  14. washeluting with a gradient of hexanes

出典と根拠

ORDレコード
ord-60962b23d7d8474689ab73bff08f0ade
出典データセット
uspto-grants-2014_06
特許番号
US08754096B2

反応ノート

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