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

HRID 932075Notes

Reaction equation

HRID 932075 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]([CH2:31][CH3:32])[CH2:25][NH:26][S:27]([CH3:30])(=[O:29])=[O:28])[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]([CH2:31][CH3:32])[CH2:25][NH:26][S:27]([CH3:30])(=[O:29])=[O:28])[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 67999447HCID 67999447, compound

Product 1

HCID 679988952-[(3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-[(2S)-1-(methanesulfonamido)butan-2-yl]-3-methyl-2-oxopiperidin-3-yl]acetic acid

Reagents, catalysts & solvents 3

HCID 6093376Ruthenium trichloride hydrateCatalystHCID 962WaterSolventHCID 5943Carbon TetrachlorideSolvent

Procedure

To a rapidly stirring solution of N-((S)-2-((3S,5R,6S)-3-allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-2-oxopiperidin-1-yl)butyl)methanesulfonamide (34 mg, 0.064 mmol; Example 91, Step C) in a mixture of water (0.55 mL), acetonitrile (0.37 mL), and CCl4 (0.37 mL) was added sodium periodate (55 mg, 0.26 mmol) and ruthenium(III) chloride hydrate (1.5 mg, 6.5 μmol). After being stirred vigorously for 20 h, the reaction was acidified (10% citric acid) and diluted with EtOAc. The insoluble material was removed by filtering through a pad of Celite® (J. T. Baker, Phillipsberg, N.J., diatomaceous earth). The filtrate was extracted (2×EtOAc) and washed (sat. aq. NaCl solution). The combined organic layers were dried (Na2SO4) and concentrated under reduced pressure. Purification by RP-HPLC (40 to 70% MeCN/H2O (0.1% TFA), a gradient elution) provided the title compound as a white foam.

Workup

  1. customThe insoluble material was removed
  2. filtrationby filtering through a pad of Celite® (J. T. Baker, Phillipsberg, N.J., diatomaceous earth)
  3. extractionThe filtrate was extracted (2×EtOAc)
  4. washwashed (sat. aq. NaCl solution)
  5. dry with materialThe combined organic layers were dried (Na2SO4)
  6. concentrationconcentrated under reduced pressure
  7. customPurification by RP-HPLC (40 to 70% MeCN/H2O (0.1% TFA)
  8. washa gradient elution)

Sources & evidence

ORD record
ord-0f45fc4835a44e19a27fc62e3b6f501c
Source dataset
uspto-grants-2016_03
Patent number
US09296736B2

Reaction notes

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