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 1048389Notes

Reaction equation

HRID 1048389 reaction equation
[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]

Participants

6

Reactant 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

Product 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

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

(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.

Workup

  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)

Sources & evidence

ORD record
ord-0521196ce2684f65a617f6b124f5b69d
Source dataset
uspto-grants-2013_10
Patent number
US08569341B2

Reaction notes

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