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

HRID 349360Notes

Reaction equation

HRID 349360 reaction equation
[CH3:1][O:2][C:3](=[O:29])[CH2:4][O:5][CH2:6][C:7]#[C:8][CH2:9][N:10]1[C:15](=[O:16])[CH2:14][CH2:13][CH2:12][C@@H:11]1/[CH:17]=[CH:18]/[C:19](=[O:28])[CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[C:23]([Cl:27])[CH:22]=1>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:29])[CH2:4][O:5][CH2:6][C:7]#[C:8][CH2:9][N:10]1[C:15](=[O:16])[CH2:14][CH2:13][CH2:12][C@@H:11]1[CH2:17][CH2:18][C:19](=[O:28])[CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[C:23]([Cl:27])[CH:22]=1

Participants

4

Reactant 1

HCID 11212242(4-{(R)-2-[(E)-4-(3-Chlorophenyl)-3-oxo-but-1-enyl]-6-oxo-piperidin-1-yl}-but-2-ynyloxy)-acetic acid methyl ester

Product 1

HCID 67011018(4-{(R)-2-[4-(3-Chlorophenyl)-3-oxo-butyl]-6-oxo-piperidin-1-yl}-but-2-ynyloxy)-acetic acid methyl esterYield 34%

Reagents, catalysts & solvents 2

HCID 11982471Stryker's reagentCatalystHCID 1140TolueneSolvent

Procedure

A solution of (4-{(R)-2-[(E)-4-(3-chlorophenyl)-3-oxo-but-1-enyl]-6-oxo-piperidin-1-yl}-but-2-ynyloxy)-acetic acid methyl ester (35 mg, 0.084 mmol) in toluene (2 mL) was added via cannula to a round-bottomed flask containing hydrido(triphenylphosphine)copper(I) hexamer (164 mg, 0.084 mmol) at −40° C. under nitrogen. The reaction was allowed to warm to rt and stirred for 3 h. The reaction was quenched with NH4OH/NH4Cl (1:1, 5 mL) and extracted with EtOAc (3×7 mL). The combined extracts were dried (MgSO4), filtered and concentrated in vacuo. Purification of the residue by flash column chromatography on silica gel (20% →50% EtOAc/CH2Cl2, gradient) followed by preparative thin layer chromatography (silica, 80% EtOAc/CH2Cl2) afforded 12 mg (34%) of the title compound.

Workup

  1. customThe reaction was quenched with NH4OH/NH4Cl (1:1, 5 mL)
  2. extractionextracted with EtOAc (3×7 mL)
  3. dry with materialThe combined extracts were dried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customPurification of the residue by flash column chromatography on silica gel (20% →50% EtOAc/CH2Cl2, gradient)

Sources & evidence

ORD record
ord-8db06ea71bb04203ac012c3f252f1d84
Source dataset
uspto-grants-2007_02
Patent number
US07179820B2

Reaction notes

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