Toluene → vinyl ether (3S,5R,6S)-3-allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((S,E)-1-methoxypent-1-en-3-yl)-3-methylpiperidin-2-one

HRID 932076Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 932076
[Cl-].[CH3:2][O:3]C[P+](C1C=CC=CC=1)(C1C=CC=CC=1)[C:6]1C=CC=C[CH:7]=1.C[Si]([N-][Si](C)(C)C)(C)C.[K+].[C:34]1(C)C=CC=C[CH:35]=1.[CH2:41]([C@@:44]1([CH3:70])[CH2:49][C@H:48]([C:50]2[CH:55]=[CH:54][CH:53]=[C:52]([Cl:56])[CH:51]=2)[C@@H:47]([C:57]2[CH:62]=[CH:61][C:60]([Cl:63])=[CH:59][CH:58]=2)[N:46]([C@@H:64]([CH2:67][CH3:68])[CH:65]=[O:66])[C:45]1=[O:69])[CH:42]=[CH2:43]>C1COCC1>[CH2:41]([C@@:44]1([CH3:70])[CH2:49][C@H:48]([C:50]2[CH:55]=[CH:54][CH:53]=[C:52]([Cl:56])[CH:51]=2)[C@@H:47]([C:57]2[CH:58]=[CH:59][C:60]([Cl:63])=[CH:61][CH:62]=2)[N:46]([C@@H:64]([CH2:34][CH3:35])/[CH:67]=[CH:68]/[O:3][CH3:2])[C:45]1=[O:69])[CH:42]=[CH2:43].[CH:6]([O:64][CH:65]=[CH2:66])=[CH2:7]

Komponenten

6

Edukt 4

HCID 1140TolueneHCID 2723798Methoxymethyl-triphenylphosphonium chlorideHCID 3251421Potassium bis(trimethylsilyl)amideHCID 58573909(S)-2-((3S,5R,6S)-3-Allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-2-oxopiperidin-1-yl)butanal

Produkt 1

HCID 86660729vinyl ether (3S,5R,6S)-3-allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((S,E)-1-methoxypent-1-en-3-yl)-3-methylpiperidin-2-one

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel2×

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

(Methoxymethyl)triphenylphosphonium chloride was dried at 80° C. under vacuum for 3 h. To a solution of the dried (methoxymethyl)triphenylphosphonium chloride (1.96 g, 5.71 mmol) in THF (10 mL) was added 0.5 M KHMDS in toluene (10.2 mL, 5.08 mmol) at −78° C. The color of the solution turned blood red in color. After stirring at 0° C. for 30 min., a solution of (S)-2-((3S,5R,6S)-3-allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-2-oxopiperidin-1-yl)butanal (Example 91, Step C; 564 mg, 1.27 mmol) in THF (10.1 mL) was added at 0° C. dropwise. After being stirred at rt for overnight, the reaction was quenched (sat NH4Cl solution), extracted (2×EtOAc), and washed (sat. aq. NaCl solution). The combined organic layers were dried (Na2SO4) and concentrated under reduced pressure. Purification by chromatography on silica gel (SiO2, 40 g, 15% and 20% EtOAc/Hexanes) provided the vinyl ether (3S,5R,6S)-3-allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((S,E)-1-methoxypent-1-en-3-yl)-3-methylpiperidin-2-one. To a solution of (3S,5R,6S)-3-allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((S,E)-1-methoxypent-1-en-3-yl)-3-methylpiperidin-2-one prepared above in acetonitrile (7.8 mL) was added 3 N hydrochloric acid (4.4 mL, 13 mmol) and the resulting solution was stirred at rt for 1.5 h. Then, the reaction was extracted (2×EtOAc), and washed (sat. aq. NaCl solution). The combined organic layers were dried (Na2SO4) and concentrated under reduced pressure to provide the title compound as a pale yellow film.

Aufarbeitung

  1. dry with material(Methoxymethyl)triphenylphosphonium chloride was dried at 80° C. under vacuum for 3 h
  2. stirringAfter being stirred at rt for overnight
  3. customthe reaction was quenched (sat NH4Cl solution)
  4. extractionextracted (2×EtOAc)
  5. washwashed (sat. aq. NaCl solution)
  6. dry with materialThe combined organic layers were dried (Na2SO4)
  7. concentrationconcentrated under reduced pressure
  8. customPurification by chromatography on silica gel (SiO2, 40 g, 15% and 20% EtOAc/Hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-279dc74047f64f718641adb4eff2c827
Quelldatensatz
uspto-grants-2016_03
Patentnummer
US09296736B2

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