Hydrochloric Acid → 2-((3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-2-oxo-1-(pentan-3-yl)piperidin-3-yl)acetic acid

HRID 931970Notes

Reaction equation

HRID 931970 reaction equation
[CH2:1]([C@@:4]1(C)[CH2:9][C@H:8]([C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([Cl:16])[CH:11]=2)[C@@H:7]([C:17]2[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][CH:18]=2)[N:6]([CH:24]([CH2:27][CH3:28])[CH2:25][CH3:26])[C:5]1=[O:29])C=C.C(Cl)(Cl)(Cl)Cl.I([O-])(=O)(=O)=O.[Na+].Cl.CC[O:45][C:46]([CH3:48])=[O:47]>C(#N)C.O.[Ru](Cl)(Cl)Cl.O>[Cl:16][C:12]1[CH:11]=[C:10]([C@@H:8]2[C@@H:7]([C:17]3[CH:18]=[CH:19][C:20]([Cl:23])=[CH:21][CH:22]=3)[N:6]([CH:24]([CH2:27][CH3:28])[CH2:25][CH3:26])[C:5](=[O:29])[C@:4]([CH2:48][C:46]([OH:45])=[O:47])([CH3:1])[CH2:9]2)[CH:15]=[CH:14][CH:13]=1

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 5943Carbon TetrachlorideHCID 8857Ethyl AcetateHCID 23667635Sodium periodateHCID 58573148(3S,5R,6S)-3-allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-1-(pentan-3-yl)piperidin-2-one

Product 1

HCID 565911372-((3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-2-oxo-1-(pentan-3-yl)piperidin-3-yl)acetic acid

Reagents, catalysts & solvents 3

HCID 6093376Ruthenium trichloride hydrateCatalystHCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

To a solution of 725 mg (1.63 mmol) of (3S,5R,6S)-3-allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-1-(pentan-3-yl)piperidin-2-one (Example 3, Step A) in a mixture of acetonitrile (4 mL), carbon tetrachloride (4 mL) and water (5.9 mL) added 1.40 g (6.53 mmol) of sodium periodate followed by 44 mg (0.20 mmol) of ruthenium(III) chloride hydrate. The dark brown biphasic mixture was stirred vigorously at room temperature for 21 h, and then was acidified with 1 N HCl. The mixture was diluted with EtOAc and filtered through a pad of Celite® (J. T. Baker, Phillipsberg, N.J., diatomaceous earth). After filtration, the layers were separated and the aqueous layer was extracted with EtOAc (1×). The combined organic layers were washed with saturated aqueous sodium chloride (1×), then were dried over Na2SO4, filtered and the filtrate was concentrated. Purification of the residue by flash chromatography on silica gel (0 to 25% MeOH/DCM, gradient elution) provided the title compound as a white solid.

Workup

  1. filtrationfiltered through a pad of Celite® (J. T. Baker, Phillipsberg, N.J., diatomaceous earth)
  2. filtrationAfter filtration
  3. customthe layers were separated
  4. extractionthe aqueous layer was extracted with EtOAc (1×)
  5. washThe combined organic layers were washed with saturated aqueous sodium chloride (1×)
  6. dry with materialwere dried over Na2SO4
  7. filtrationfiltered
  8. concentrationthe filtrate was concentrated
  9. customPurification of the residue by flash chromatography on silica gel (0 to 25% MeOH/DCM, gradient elution)

Sources & evidence

ORD record
ord-474c459ed4df45ba831f0d0be0c96a0c
Source dataset
uspto-grants-2016_03
Patent number
US09296736B2

Reaction notes

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