Water → 2-((3R,5R,6S)-5-(3-Chlorophenyl)-6-(4-chlorophenyl)-1-((1S,2S,3R)-2,3-dihydroxycyclopentyl)-3-methyl-2-oxopiperidin-3-yl)acetic acid

HRID 932011Notes

Reaction equation

HRID 932011 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:8]2[C@@H:13]([C:14]3[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=3)[N:12]([CH:21]3[CH2:25][CH2:24][CH:23]=[CH:22]3)[C:11](=[O:26])[C@:10]([CH2:28][C:29]([OH:31])=[O:30])([CH3:27])[CH2:9]2)[CH:5]=[CH:6][CH:7]=1.[OH2:32].CC([OH:37])(C)C.C[N+]1([O-])CCOCC1>C1COCC1.[Os](=O)(=O)(=O)=O>[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:8]2[C@@H:13]([C:14]3[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=3)[N:12]([C@H:21]3[CH2:25][CH2:24][C@@H:23]([OH:32])[C@H:22]3[OH:37])[C:11](=[O:26])[C@:10]([CH2:28][C:29]([OH:31])=[O:30])([CH3:27])[CH2:9]2)[CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 962Water2×HCID 6386tert-ButanolHCID 82029Methyl morpholine oxideHCID 585732432-((3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-(cyclopent-2-enyl)-3-methyl-2-oxopiperidin-3-yl)acetic acid

Product 1

HCID 585732412-((3R,5R,6S)-5-(3-Chlorophenyl)-6-(4-chlorophenyl)-1-((1S,2S,3R)-2,3-dihydroxycyclopentyl)-3-methyl-2-oxopiperidin-3-yl)acetic acid

Reagents, catalysts & solvents 2

HCID 30318Osmium TetroxideCatalystHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 2-((3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-(cyclopent-2-enyl)-3-methyl-2-oxopiperidin-3-yl)acetic acid (Example 102, Step F) (94 mg, 0.205 mmol) in THF (1.0 mL) was added water (0.25 mL) and tBuOH (0.2 mL) at room temperature. NMO (36.0 mg, 0.308 mmol) was added followed by osmium tetroxide (4% aq) (1.303 μL, 0.205 μmol). The reaction mixture was stirred at room temperature for 24 h. Water (10 mL) was added and the mixture was extracted with DCM twice. The organic layers were combined and dried over Na2SO4 and concentrated under reduced pressure. The residue, containing a mixture of three stereoisomers, was purified by reversed phase preparatory HPLC (column: Gemini-NX C18 5 um column; Phenomonex, Torrance, Calif.; eluent: 30 to 50% MeCN +0.1% TFA in water +0.1% TFA, over 20 minutes) to provide the title compound as the first eluting isomer.

Workup

  1. extractionthe mixture was extracted with DCM twice
  2. dry with materialdried over Na2SO4
  3. concentrationconcentrated under reduced pressure
  4. additionThe residue, containing
  5. additiona mixture of three stereoisomers
  6. customwas purified by reversed phase preparatory HPLC (column: Gemini-NX C18 5 um column; Phenomonex, Torrance, Calif.; eluent: 30 to 50% MeCN +0.1% TFA in water +0.1% TFA, over 20 minutes)

Sources & evidence

ORD record
ord-97bb0a7f378446739a3b134a26a10bfc
Source dataset
uspto-grants-2016_03
Patent number
US09296736B2

Reaction notes

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