(S)-2-((3S,5R,6S)-3-Allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-2-oxopiperidin-1-yl)-3-methylbutanal → (3S,5R,6S)-3-Allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((S)-2-hydroxy-4-methylpentan-3-yl)-3-methylpiperidin-2-one

HRID 932214Notes

Reaction equation

HRID 932214 reaction equation
[CH3:1][Mg]Br.[CH2:4]([C@@:7]1([CH3:34])[CH2:12][C@H:11]([C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([Cl:19])[CH:14]=2)[C@@H:10]([C:20]2[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][CH:21]=2)[N:9]([C@@H:27]([CH:30]([CH3:32])[CH3:31])[CH:28]=[O:29])[C:8]1=[O:33])[CH:5]=[CH2:6]>C1COCC1>[CH2:4]([C@@:7]1([CH3:34])[CH2:12][C@H:11]([C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([Cl:19])[CH:14]=2)[C@@H:10]([C:20]2[CH:21]=[CH:22][C:23]([Cl:26])=[CH:24][CH:25]=2)[N:9]([CH:27]([CH:30]([CH3:31])[CH3:32])[C@@H:28]([OH:29])[CH3:1])[C:8]1=[O:33])[CH:5]=[CH2:6]

Participants

4

Reactant 2

HCID 58573712(S)-2-((3S,5R,6S)-3-Allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-2-oxopiperidin-1-yl)-3-methylbutanalHCID 178418573HCID 178418573, compound

Product 1

HCID 67998773(3S,5R,6S)-3-Allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((S)-2-hydroxy-4-methylpentan-3-yl)-3-methylpiperidin-2-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Methylmagnesium bromide (1.4 mL, 1.960 mmol, 1.4 M in 1:3 THF:toluene) was added by syringe to a solution under nitrogen of pre-dried (S)-2-((3S,5R,6S)-3-allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-2-oxopiperidin-1-yl)-3-methylbutanal (Example 261, Step 1,286 mg, 0.624 mmol) in THF (6.5 mL) at 0° C. The ice bath was removed. After 2 h, the solution was recooled to 0° C. and quenched by careful addition of saturated ammonium chloride solution. The resulting mixture was extracted with ethyl acetate. The organic layer was washed with sat. aq. NaCl solution, dried over sodium sulfate, filtered, and concentrated. The residue was purified by chromatography on silica, eluting with a gradient of 0 to 40% ethyl acetate in hexanes. Fractions containing the desired product were combined and re-purified to give the title compound as a mixture of diastereomeric alcohols) as a white foam. MS (ESI) m/z=474 [M+H]+.

Workup

  1. customThe ice bath was removed
  2. customwas recooled to 0° C.
  3. customquenched by careful addition of saturated ammonium chloride solution
  4. extractionThe resulting mixture was extracted with ethyl acetate
  5. washThe organic layer was washed with sat. aq. NaCl solution
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by chromatography on silica
  10. washeluting with a gradient of 0 to 40% ethyl acetate in hexanes
  11. additionFractions containing the desired product
  12. customre-purified

Sources & evidence

ORD record
ord-a766ab901a814d228237abb0810e5604
Source dataset
uspto-grants-2016_03
Patent number
US09296736B2

Reaction notes

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