(3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)-1-((S)-1-(ethylsulfonyl)pentan-3-yl)-3-methylpiperidin-2-one → 2-((3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((S)-1-(ethylsulfonyl)pentan-3-yl)-3-methyl-2-oxopiperidin-3-yl)acetic acid

HRID 1048466Notes

Reaction equation

HRID 1048466 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]([C@@H:21]([CH2:29][CH3:30])[CH2:22][CH2:23][S:24]([CH2:27][CH3:28])(=[O:26])=[O:25])[C:11](=[O:31])[C@:10]([CH2:33]C3COC(C)(C)O3)([CH3:32])[CH2:9]2)[CH:5]=[CH:6][CH:7]=1.C[C:42](C)=[O:43].[OH:45]S(O)(=O)=O.O=[Cr](=O)=O>C1COCC1>[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]([CH2:29][CH3:30])[CH2:22][CH2:23][S:24]([CH2:27][CH3:28])(=[O:25])=[O:26])[C:11](=[O:31])[C@:10]([CH2:33][C:42]([OH:43])=[O:45])([CH3:32])[CH2:9]2)[CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 58573576(3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)-1-((S)-1-(ethylsulfonyl)pentan-3-yl)-3-methylpiperidin-2-oneHCID 131709961Jones' reagent

Product 1

HCID 585739932-((3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((S)-1-(ethylsulfonyl)pentan-3-yl)-3-methyl-2-oxopiperidin-3-yl)acetic acid

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of (3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)-1-((S)-1-(ethylsulfonyl)pentan-3-yl)-3-methylpiperidin-2-one (70.0 mg, 0.115 mmol; Example 202, Step C) in THF (1.15 mL) at 25° C. was added a solution of Jones' Reagent (chromium (VI) oxide) (138 μL, 0.172 mmol) and the reaction mixture was stirred for 1 hour. The reaction mixture was partitioned between water and EtOAc (2×), and then the combined organic layers were dried over Na2SO4, filtered and the filtrate was concentrated under reduced pressure. Purification of the residue by reverse phase high-pressure liquid chromatography (Eclipse column (Agilient Technologies, Santa Clara, Calif.), eluent: 30-75% acetonitrile/water) provided the title compound as an off-white solid.

Workup

  1. customThe reaction mixture was partitioned between water and EtOAc (2×)
  2. dry with materialthe combined organic layers were dried over Na2SO4
  3. filtrationfiltered
  4. concentrationthe filtrate was concentrated under reduced pressure
  5. customPurification of the residue by reverse phase high-pressure liquid chromatography (Eclipse column (Agilient Technologies, Santa Clara, Calif.), eluent: 30-75% acetonitrile/water)

Sources & evidence

ORD record
ord-802297f2b034431b969882a477e592e5
Source dataset
uspto-grants-2013_10
Patent number
US08569341B2

Reaction notes

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