Citric Acid → HCID 67999791, compound

HRID 932216Notes

Reaction equation

HRID 932216 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:44]2[CH2:46][CH2:45]2)[CH2:25][O:26][Si:27]([C:40]([CH3:43])([CH3:42])[CH3:41])([C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)[C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[C:5]1=[O:47])C=C.I([O-])(=O)(=O)=O.[Na+].C(O)(=O)CC(CC(O)=O)(C(O)=O)O.CC[O:70][C:71]([CH3:73])=[O:72]>O.O.[Ru](Cl)(Cl)Cl.C(Cl)(Cl)(Cl)Cl.C(#N)C>[Si:27]([O:26][CH2:25][C@@H:24]([N:6]1[C@H:7]([C:17]2[CH:18]=[CH:19][C:20]([Cl:23])=[CH:21][CH:22]=2)[C@@H:8]([C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([Cl:16])[CH:11]=2)[CH2:9][C@@:4]([CH2:73][C:71]([OH:70])=[O:72])([CH3:1])[C:5]1=[O:47])[CH:44]1[CH2:45][CH2:46]1)([C:40]([CH3:42])([CH3:43])[CH3:41])([C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1

Participants

9

Reactant 4

HCID 311Citric AcidHCID 8857Ethyl AcetateHCID 23667635Sodium periodate2×HCID 67999225HCID 67999225, compound

Product 1

HCID 67999791HCID 67999791, compound

Reagents, catalysts & solvents 4

HCID 6093376Ruthenium trichloride hydrateCatalyst2×HCID 962WaterSolvent2×HCID 5943Carbon TetrachlorideSolvent2×HCID 6342AcetonitrileSolvent2×

Procedure

To a rapidly stirring solution of (3S,5R,6S)-3-allyl-1-((S)-2-(tert-butyldiphenylsilyloxy)-1-cyclopropylethyl)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methylpiperidin-2-one (1450 mg, 2.08 mmol; Example 251, Step D) in a mixture of water (11 mL), acetonitrile (7.2 mL), and CCl4 (7.2 mL) was added sodium periodate (1780 mg, 8.32 mmol), followed by ruthenium (III) chloride hydrate (47 mg, 0.21 mmol). After being stirred vigorously for 16 h, additional water (5.4 mL), acetonitrile (3.6 mL), and CCl4 (3.6 mL) were added and to the resulting clear dark solution as was added additional sodium periodate (890 mg, 4.16 mmol) and ruthenium (III) chloride hydrate (24 mg, 0.10 mmol). After being stirred vigorously for additional 4 h, the reaction was acidified (10% citric acid) and diluted (EtOAc). The reaction mixture was filtered through pad of Celite® (J. T. Baker, Phillipsberg, N.J., diatomaceous earth) and the filtrate was extracted (2×EtOAc). The combined organic layers were washed (brine), dried (Na2SO4), and concentrated under the reduced pressure. Purification of the residue by chromatography on silica gel (80 g SiO2, 30%, 40%, and 50% EtOAc/Hex) provided the title compound as a pale yellow foam.

Workup

  1. stirringAfter being stirred vigorously for additional 4 h
  2. filtrationThe reaction mixture was filtered through pad of Celite® (J. T. Baker, Phillipsberg, N.J., diatomaceous earth)
  3. extractionthe filtrate was extracted (2×EtOAc)
  4. washThe combined organic layers were washed (brine)
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated under the reduced pressure
  7. customPurification of the residue by chromatography on silica gel (80 g SiO2, 30%, 40%, and 50% EtOAc/Hex)

Sources & evidence

ORD record
ord-dc8ab573ead3465a8281b0bc3f5c6984
Source dataset
uspto-grants-2016_03
Patent number
US09296736B2

Reaction notes

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