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

HRID 349366Notes

Reaction equation

HRID 349366 reaction equation
[CH3:1][O:2][C:3](=[O:28])[CH2:4][O:5][CH2:6][C:7]#[C: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]>C1(C)C=CC=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.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][C:7]#[C: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 69020236{4-[(R)-2-Oxo-6-((E)-3-oxo-4-phenyl-but-1-enyl)-piperidin-1-yl]-but-2-ynyloxy}-acetic acid methyl ester

Product 1

HCID 69022436{4-[(R)-2-Oxo-6-(3-oxo-4-phenyl-butyl)-piperidin-1-yl]-but-2-ynyloxy}-acetic acid methyl esterYield 78%

Reagents, catalysts & solvents 2

HCID 11982471Stryker's reagentCatalystHCID 1140TolueneSolvent

Procedure

A solution of {4-[(R)-2-Oxo-6-((E)-3-oxo-4-phenyl-but-1-enyl)-piperidin-1-yl]-but-2-ynyloxy}-acetic acid methyl ester (30 mg, 0.078 mmol) in toluene (2 mL) was added via cannula to a round-bottomed flask containing hydrido(triphenylphosphine)copper(I) hexamer (154 mg, 0.078 mmol) at −40° C. under nitrogen. The reaction was allowed to warm to rt and stirred for 2.5 h. The reaction was quenched with NH4OH/NH4Cl (1:1, 8 mL) and extracted with EtOAc (3×10 mL). The combined extracts were dried washed with brine (10 mL) then dried (Na2SO4), filtered and concentrated in vacuo. Purification of the residue by flash column chromatography on silica gel (20% →40% EtOAc/CH2Cl2, gradient) afforded 23.4 mg (78%) of the title compound.

Workup

  1. customThe reaction was quenched with NH4OH/NH4Cl (1:1, 8 mL)
  2. extractionextracted with EtOAc (3×10 mL)
  3. customThe combined extracts were dried
  4. washwashed with brine (10 mL)
  5. dry with materialthen dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customPurification of the residue by flash column chromatography on silica gel (20% →40% EtOAc/CH2Cl2, gradient)

Sources & evidence

ORD record
ord-c58a072696324aba886bcaabc1a7a8c4
Source dataset
uspto-grants-2007_02
Patent number
US07179820B2

Reaction notes

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