Citric Acid → 2-((3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-1-((S)-6-methyl-4-oxoheptan-3-yl)-2-oxopiperidin-3-yl)acetic acid

HRID 932150Notes

Reaction equation

HRID 932150 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]([C@H:24]([CH:27]([OH:32])[CH2:28][CH:29]([CH3:31])[CH3:30])[CH2:25][CH3:26])[C:5]1=[O:33])C=C.C(#N)C.I([O-])(=O)(=O)=O.[Na+].C(O)(=O)CC(CC(O)=O)(C(O)=O)O.CC[O:59][C:60]([CH3:62])=[O:61]>O.O.[Ru](Cl)(Cl)Cl.C(Cl)(Cl)(Cl)Cl>[Cl:16][C:12]1[CH:11]=[C:10]([C@@H:8]2[C@@H:7]([C:17]3[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][CH:18]=3)[N:6]([C@H:24]([C:27](=[O:32])[CH2:28][CH:29]([CH3:30])[CH3:31])[CH2:25][CH3:26])[C:5](=[O:33])[C@:4]([CH2:62][C:60]([OH:59])=[O:61])([CH3:1])[CH2:9]2)[CH:15]=[CH:14][CH:13]=1

Participants

9

Reactant 5

HCID 311Citric AcidHCID 6342AcetonitrileHCID 8857Ethyl AcetateHCID 23667635Sodium periodateHCID 58573939HCID 58573939, compound

Product 1

HCID 585740052-((3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-1-((S)-6-methyl-4-oxoheptan-3-yl)-2-oxopiperidin-3-yl)acetic acid

Reagents, catalysts & solvents 3

HCID 6093376Ruthenium trichloride hydrateCatalystHCID 962WaterSolventHCID 5943Carbon TetrachlorideSolvent

Procedure

To a rapidly stirring solution of 120 mg (0.239 mmol) of (3S,5R,6S)-3-allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((3S)-4-hydroxy-6-methylheptan-3-yl)-3-methylpiperidin-2-one (Example 204, Step A) in a mixture of 1.5 mL of water, 1.0 mL of acetonitrile and 1.0 mL of CCl4 was added sodium periodate (204 mg, 0.995 mmol), followed by ruthenium(III) chloride hydrate (5.38 mg, 0.024 mmol). After being stirred vigorously for 2 h, the reaction was acidified (10% citric acid) and diluted with EtOAc. The reaction mixture was filtered through Celite® (J. T. Baker, Phillipsberg, N.J., diatomaceous earth) and the filtrate was extracted with EtOAc. The combined organic layers were washed with sat. NaCl solution, dried over Na2SO4, filtered and the filtrate was concentrated under reduced pressure. The residue was purified by the flash chromatography on silica gel (eluent: 10 to 20% iPrOH/hexane, gradient elution) to provide the title compound as a white solid.

Workup

  1. filtrationThe reaction mixture was filtered through Celite® (J. T. Baker, Phillipsberg, N.J., diatomaceous earth)
  2. extractionthe filtrate was extracted with EtOAc
  3. washThe combined organic layers were washed with sat. NaCl solution
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationthe filtrate was concentrated under reduced pressure
  7. customThe residue was purified by the flash chromatography on silica gel (eluent: 10 to 20% iPrOH/hexane, gradient elution)

Sources & evidence

ORD record
ord-3dd7e25b5a2046f185ebfcf8214a77a2
Source dataset
uspto-grants-2016_03
Patent number
US09296736B2

Reaction notes

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