Citric Acid → HCID 67999477, compound

HRID 932230Notes

Reaction equation

HRID 932230 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:34]([CH3:36])[CH3:35])[CH2:25][N:26]([CH3:33])[S:27]([CH:30]2[CH2:32][CH2:31]2)(=[O:29])=[O:28])[C:5]1=[O:37])C=C.I([O-])(=O)(=O)=O.[Na+].O.C(O)(=O)CC(CC(O)=O)(C(O)=O)O.[C:59]([O:62]CC)(=[O:61])[CH3:60]>C(#N)C.C(Cl)(Cl)(Cl)Cl.O.[Ru](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]([CH:34]([CH3:35])[CH3:36])[CH2:25][N:26]([CH3:33])[S:27]([CH:30]3[CH2:31][CH2:32]3)(=[O:28])=[O:29])[C:5](=[O:37])[C@:4]([CH2:60][C:59]([OH:62])=[O:61])([CH3:1])[CH2:9]2)[CH:15]=[CH:14][CH:13]=1

Participants

9

Reactant 5

HCID 311Citric AcidHCID 962WaterHCID 8857Ethyl AcetateHCID 23667635Sodium periodateHCID 68000099HCID 68000099, compound

Product 1

HCID 67999477HCID 67999477, compound

Reagents, catalysts & solvents 3

HCID 6093376Ruthenium trichloride hydrateCatalystHCID 5943Carbon TetrachlorideSolventHCID 6342AcetonitrileSolvent

Procedure

A mixture of N-((S)-2-((3S,5R,6S)-3-allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-2-oxopiperidin-1-yl)-3-methylbutyl)-N-methylcyclopropanesulfonamide (Example 295, Step A, 112.5 mg, 0.195 mmol), sodium periodate (170 mg, 0.795 mmol), and ruthenium(III) chloride hydrate (6 mg, 0.023 mmol) in acetonitrile (1.0 mL), carbon tetrachloride (1.0 mL), and water (1.5 mL) was vigorously stirred at ambient temperature overnight. The reaction mixture was acidified with aqueous citric acid (10% by weight), diluted in ethyl acetate, and filtered through a pad of Celite® (J. T. Baker, Phillipsberg, N.J., diatomaceous earth). The filtrate was partitioned between 2 M aqueous HCl and ethyl acetate. Combined organics were washed with brine, dried over sodium sulfate, filtered, and concentrated in vacuo to a residue that was purified by preparative HPLC (Sunfire™ Prep C18 OBD 10 μm column, 30×150 mm, Waters, Milford, Mass.) eluting with a gradient of 50 to 100% acetonitrile in water (0.1% trifluoroacetic acid in both solvents). Chromatography fractions containing the product were stripped of volatiles, redissolved in minimal volumes of acetonitrile and water, frozen, and lyophilized to give the product as a white solid.

Workup

  1. filtrationfiltered through a pad of Celite® (J. T. Baker, Phillipsberg, N.J., diatomaceous earth)
  2. customThe filtrate was partitioned between 2 M aqueous HCl and ethyl acetate
  3. washCombined organics were washed with brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo to a residue that
  7. customwas purified by preparative HPLC (Sunfire™ Prep C18 OBD 10 μm column, 30×150 mm, Waters, Milford, Mass.)
  8. washeluting with a gradient of 50 to 100% acetonitrile in water (0.1% trifluoroacetic acid in both solvents)
  9. additionChromatography fractions containing the product
  10. dissolutionredissolved in minimal volumes of acetonitrile and water
  11. temperaturefrozen

Sources & evidence

ORD record
ord-8b4f5459a6e545448dbaf7f27faa7067
Source dataset
uspto-grants-2016_03
Patent number
US09296736B2

Reaction notes

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