Toluene → (3S,5R,6S)-3-Allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((S)-1-methoxy-2-methylpent-1-en-3-yl)-3-methylpiperidin-2-one

HRID 932094Notes

Reaction equation

HRID 932094 reaction equation
[Cl-:1].[CH3:2][O:3]C[P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C[Si]([N-][Si](C)(C)C)(C)C.[K+].[C:34]1(C)C=CC=CC=1.[CH2:41]([C@@:44]1([CH3:71])[CH2:49][C@H:48]([C:50]2[CH:55]=[CH:54][CH:53]=[C:52](Cl)[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]([CH2:68][CH3:69])[C:65](=O)[CH3:66])[C:45]1=[O:70])[CH:42]=[CH2:43]>C1COCC1>[CH2:41]([C@@:44]1([CH3:71])[CH2:49][C@H:48]([C:50]2[CH:51]=[CH:52][CH:53]=[C:54]([Cl:1])[CH:55]=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]([CH2:68][CH3:69])[C:65]([CH3:34])=[CH:66][O:3][CH3:2])[C:45]1=[O:70])[CH:42]=[CH2:43]

Participants

6

Reactant 4

HCID 1140TolueneHCID 2723798Methoxymethyl-triphenylphosphonium chlorideHCID 3251421Potassium bis(trimethylsilyl)amideHCID 58573535(3S,5R,6S)-3-Allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-1-((S)-2-oxopentan-3-yl)piperidin-2-one

Product 1

HCID 68000089(3S,5R,6S)-3-Allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((S)-1-methoxy-2-methylpent-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 2 h. To a solution of the dried (methoxymethyl)triphenylphosphonium chloride (673 mg, 1.96 mmol) in THF (3.5 mL) was added 0.5 M KHMDS in toluene (3.49 mL, 1.75 mmol) at −78° C. The solution resulted in a blood red color. After addition, the reaction was stirred at 0° C. for 30 min and a solution of (3S,5R,6S)-3-allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-1-((S)-2-oxopentan-3-yl)piperidin-2-one prepared above in Step B (200 mg, 0.436 mmol) in THF (3.5 mL) was added dropwisely at 0° C. The reaction was allowed to warm to rt and stirred for 1.5 h. Then the reaction was quenched (sat NH4Cl solution), extracted (2×EtOAc), and washed (brine). The combined organic layers were dried (Na2SO4) and concentrated under reduced pressure. Purification by combi flash (SiO2, 24 g, 15% and 20% EtOAc/Hexanes) provided the title compound as a colorless film.

Workup

  1. dry with material(Methoxymethyl)triphenylphosphonium chloride was dried at 80° C. under vacuum for 2 h
  2. customThe solution resulted in a blood red color
  3. additionAfter addition
  4. additionwas added dropwisely at 0° C
  5. temperatureto warm to rt
  6. stirringstirred for 1.5 h
  7. customThen the reaction was quenched (sat NH4Cl solution)
  8. extractionextracted (2×EtOAc)
  9. washwashed (brine)
  10. dry with materialThe combined organic layers were dried (Na2SO4)
  11. concentrationconcentrated under reduced pressure
  12. customPurification by combi flash (SiO2, 24 g, 15% and 20% EtOAc/Hexanes)

Sources & evidence

ORD record
ord-6e554feaa22b46ae88636eb780628db8
Source dataset
uspto-grants-2016_03
Patent number
US09296736B2

Reaction notes

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