{(Z)-4-[(R)-2-Oxo-6-((E)-3-oxo-4-phenyl-but-1-enyl)-piperidin-1-yl]-but-2-enyloxy}-acetic acid methyl ester → {(Z)-4-[(R)-2-Oxo-6-(3-oxo-4-phenyl-butyl)-piperidin-1-yl]-but-2-enyloxy}-acetic acid methyl ester

HRID 349343Notes

Reaction equation

HRID 349343 reaction equation
[CH3:1][O:2][C:3](=[O:28])[CH2:4][O:5][CH2:6]/[CH:7]=[CH:8]\[CH2:9][N:10]1[C@@H:15](/[CH:16]=[CH:17]/[C:18](=[O:26])[CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH2:14][CH2:13][CH2:12][C:11]1=[O:27]>CC#N.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Cu].[Cu].[Cu].[Cu].[Cu].[Cu]>[CH3:1][O:2][C:3](=[O:28])[CH2:4][O:5][CH2:6]/[CH:7]=[CH:8]\[CH2:9][N:10]1[C@@H:15]([CH2:16][CH2:17][C:18](=[O:26])[CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH2:14][CH2:13][CH2:12][C:11]1=[O:27]

Participants

4

Reactant 1

HCID 60023029{(Z)-4-[(R)-2-Oxo-6-((E)-3-oxo-4-phenyl-but-1-enyl)-piperidin-1-yl]-but-2-enyloxy}-acetic acid methyl ester

Product 1

HCID 11749537{(Z)-4-[(R)-2-Oxo-6-(3-oxo-4-phenyl-butyl)-piperidin-1-yl]-but-2-enyloxy}-acetic acid methyl esterYield 79%

Reagents, catalysts & solvents 2

HCID 11982471Stryker's reagentCatalystHCID 6342AcetonitrileSolvent

Procedure

A solution of {(Z)-4-[(R)-2-oxo-6-((E)-3-oxo-4-phenyl-but-1-enyl)-piperidin-1-yl]-but-2-enyloxy}-acetic acid methyl ester (24.6 mg, 0.064 mmol) in CH3CN (1.5 mL) was added via cannula to hydrido(triphenylphosphine)copper(I) hexamer (125 mg, 0.064 mmol) at −40° C. After 1 h at −40° C., the reaction was allowed to warm to rt. After 3 h at rt, the reaction was quenched by addition of a solution of NH4OH and saturated aqueous NH4Cl (1:1, 6 mL). The mixture was extracted with EtOAc (3×10 mL). The combined organic phase was washed with brine (20 mL), dried (Na2SO4), filtered and concentrated in vacuo. Purification of the residue by flash column chromatography on silica gel (20% →70% EtOAc/CH2Cl2, gradient) afforded 19.6 mg (79%) of the title compound.

Workup

  1. waitAfter 3 h at rt
  2. customthe reaction was quenched by addition of a solution of NH4OH and saturated aqueous NH4Cl (1:1, 6 mL)
  3. extractionThe mixture was extracted with EtOAc (3×10 mL)
  4. washThe combined organic phase was washed with brine (20 mL)
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customPurification of the residue by flash column chromatography on silica gel (20% →70% EtOAc/CH2Cl2, gradient)

Sources & evidence

ORD record
ord-c309a95323d84011ae97a1330819a3a8
Source dataset
uspto-grants-2007_02
Patent number
US07179820B2

Reaction notes

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