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 932076노트

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HRID 932076 반응식
[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]

참가 물질

6

반응물 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

생성물 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

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

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온도
0 °C

실험 절차

(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.

후처리

  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)

출처 및 근거

ORD 기록
ord-279dc74047f64f718641adb4eff2c827
출처 데이터셋
uspto-grants-2016_03
특허 번호
US09296736B2

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