Acetic Acid → trans-6-(2,5-Difluorophenyl)-1-[2-(2-fluorophenyl)ethyl]-5-nitropiperidin-2-one

HRID 241575

Reaktionsgleichung

Reaktionsgleichung von HRID 241575
[F:1][C:2]1[CH:9]=[CH:8][C:7]([F:10])=[CH:6][C:3]=1[CH:4]=O.[N+:11]([CH2:14][CH2:15][CH2:16][C:17]([O:19]C)=O)([O-:13])=[O:12].[F:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=1[CH2:28][CH2:29][NH2:30].C([O-])(=O)C.[Na+].C(O)(=O)C>C(O)C>[F:1][C:2]1[CH:9]=[CH:8][C:7]([F:10])=[CH:6][C:3]=1[C@@H:4]1[N:30]([CH2:29][CH2:28][C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][C:22]=2[F:21])[C:17](=[O:19])[CH2:16][CH2:15][C@H:14]1[N+:11]([O-:13])=[O:12]

Komponenten

7

Edukt 5

HCID 176Acetic AcidHCID 25604Methyl 4-nitrobutyrateHCID 1376632,5-DifluorobenzaldehydeHCID 517045Sodium AcetateHCID 6433572-(2-Fluorophenyl)ethylamine

Produkt 1

HCID 67389936trans-6-(2,5-Difluorophenyl)-1-[2-(2-fluorophenyl)ethyl]-5-nitropiperidin-2-one

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 702EthanolLösungsmittel

Versuchsvorschrift

To a solution of 2,5-difluorobenzaldehyde (0.765 mL, 7.04 mmol) in ethanol (15 mL) was added methyl 4-nitrobutyrate (0.901 mL, 7.04 mmol) and the mixture stirred for 5 minutes. To the reaction mixture was added 2-(2-fluorophenyl)ethylamine (0.87 mL, 7.04 mmol) and the mixture stirred for 10 minutes. To the mixture was added sodium acetate (0.577 g, 7.04 mmol) followed by glacial acetic acid (0.806 mL, 14.07 mmol) and the mixture heated at reflux temperature for 48 h. The solvent was removed in vacuo and to the yellow oil was added saturated aqueous sodium hydrogen carbonate (25 mL) and the aqueous phase extracted with ethyl acetate (4×25 mL). The combined organic phases were washed with saturated aqueous brine (1×25 mL), dried with anhydrous sodium sulfate, filtered and the solvent removed in vacuo. The yellow oil was purified by column chromatography (silica gel Biotage 40S) eluting with ethyl acetate/hexane (gradient from 0% to 60%) to give the racemic trans title compound as a yellow gum. LC/MS 379.2 (M+1).

Aufarbeitung

  1. stirringthe mixture stirred for 10 minutes
  2. temperaturethe mixture heated
  3. temperatureat reflux temperature for 48 h
  4. customThe solvent was removed in vacuo and to the yellow oil
  5. additionwas added saturated aqueous sodium hydrogen carbonate (25 mL)
  6. extractionthe aqueous phase extracted with ethyl acetate (4×25 mL)
  7. washThe combined organic phases were washed with saturated aqueous brine (1×25 mL)
  8. dry with materialdried with anhydrous sodium sulfate
  9. filtrationfiltered
  10. customthe solvent removed in vacuo
  11. customThe yellow oil was purified by column chromatography (silica gel Biotage 40S)
  12. washeluting with ethyl acetate/hexane (gradient from 0% to 60%)

Quellen und Nachweise

ORD-Eintrag
ord-c48ed4fd179a49999add4d14591782af
Quelldatensatz
uspto-grants-2014_02
Patentnummer
US08653059B2

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