p-Toluenesulfonic acid → (3EZ,5S)-1-([1,1'-biphenyl]-4-ylcarbonyl)-5-(1,2,4-oxadiazol-3-yl)-3-pyrrolidinone O-methyloxime

HRID 1242620Notes

Reaction equation

HRID 1242620 reaction equation
[C:1]1([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH:6]=[CH:5][C:4]([C:7]([N:9]2[CH2:13][C:12](=[N:14][O:15][CH3:16])[CH2:11][C@H:10]2[C:17](=[N:19][OH:20])[NH2:18])=[O:8])=[CH:3][CH:2]=1.[C:27]1(C)C=CC(S(O)(=O)=O)=CC=1>C[C@H](NC([C@H]1N(C([C@@H](NC([C@@H](N)CC2C=CC(O)=CC=2)=O)CC(O)=O)=O)CCC1)=O)C(N1[C@H](C(N2[C@H](C(N3[C@H](C(N4[C@H](C(N5[C@H](C(N6[C@H](C(O)=O)CCC6)=O)CCC5)=O)CCC4)=O)CCC3)=O)CCC2)=O)CCC1)=O>[CH3:16][O:15][N:14]=[C:12]1[CH2:11][C@@H:10]([C:17]2[N:18]=[CH:27][O:20][N:19]=2)[N:9]([C:7]([C:4]2[CH:3]=[CH:2][C:1]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)=[CH:6][CH:5]=2)=[O:8])[CH2:13]1

Participants

4

Reactant 2

HCID 6101p-Toluenesulfonic acidHCID 90995821(2S,4EZ)-1-([1,1'-biphenyl]-4-ylcarbonyl)-N'-hydroxy-4-(methoxyimino)-2-pyrrolidinecarboximidamide2×

Product 1

HCID 91554025(3EZ,5S)-1-([1,1'-biphenyl]-4-ylcarbonyl)-5-(1,2,4-oxadiazol-3-yl)-3-pyrrolidinone O-methyloxime

Reagents, catalysts & solvents 1

HCID 5488810Peptide oostatic hormoneSolvent

Procedure

To a suspension of (2S,4EZ)-1-([1,1′-biphenyl]-4-ylcarbonyl)-N′-hydroxy-4-(methoxyimino)-2-pyrrolidinecarboximidamide (Intermediate 8, 170 mg, 0.48 mmol) in TMOF (20 ml), a catalytic amount of p-toluenesulfonic acid was added and the reaction mixture was heated to reflux for 16 h. TMOF was then evaporated in vacuo and the residue dissolved in DCM (15 mls). This was washed with NaHCO3(aq) (2×15 ml), dried over MgSO4 and evaporated in vacuo. Silica gel chromatography eluting with 15% EtOAc in hexanes gave the desired product, (3EZ,5S)-1-([1,1′-biphenyl]-4-ylcarbonyl)-5-(1,2,4-oxadiazol-3-yl)-3-pyrrolidinone O-methyloxime (59 mg).

Workup

  1. temperaturethe reaction mixture was heated
  2. temperatureto reflux for 16 h
  3. customTMOF was then evaporated in vacuo
  4. dissolutionthe residue dissolved in DCM (15 mls)
  5. washThis was washed with NaHCO3(aq) (2×15 ml)
  6. dry with materialdried over MgSO4
  7. customevaporated in vacuo
  8. washSilica gel chromatography eluting with 15% EtOAc in hexanes

Sources & evidence

ORD record
ord-602bd5f5656a4d568db27d9efae2e1f8
Source dataset
uspto-grants-2006_10
Patent number
US07115639B2

Reaction notes

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