Sodium Carbonate → (3Ez,5s)-5-{5-[(1s,2r)-1-amino-2-hydroxypropyl]-1,2,4-oxadiazol-3-yl}-1-([1,1'-biphenyl]-4-ylcarbonyl)-3-pyrrolidinone o-methyloxime

HRID 1242601Notes

Reaction equation

HRID 1242601 reaction equation
C([O:5][C@H:6]([CH3:43])[C@@H:7]([C:16]1[O:20][N:19]=[C:18]([C@@H:21]2[CH2:25][C:24](=[N:26][O:27][CH3:28])[CH2:23][N:22]2[C:29]([C:31]2[CH:36]=[CH:35][C:34]([C:37]3[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=3)=[CH:33][CH:32]=2)=[O:30])[N:17]=1)[NH:8]C(OC(C)(C)C)=O)(C)(C)C.C(O)(C(F)(F)F)=O.C(Cl)Cl.C(=O)([O-])[O-].[Na+].[Na+]>>[CH3:28][O:27][N:26]=[C:24]1[CH2:25][C@@H:21]([C:18]2[N:17]=[C:16]([C@@H:7]([NH2:8])[C@H:6]([OH:5])[CH3:43])[O:20][N:19]=2)[N:22]([C:29]([C:31]2[CH:32]=[CH:33][C:34]([C:37]3[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=3)=[CH:35][CH:36]=2)=[O:30])[CH2:23]1

Participants

4

Reactant 3

HCID 10340Sodium CarbonateHCID 21863450Trifluoroacetic acid methylene chlorideHCID 587145874-{[(2S,4EZ)-2-(5-{(1S,2R)-2-tert-butoxy-1-[(tert-butoxycarbonyl) amino]propyl}-1,2,4-oxadiazol-3-yl)-4-(methoxyimino)pyrrolidinyl]carbonyl}-1,1'-biphenyl

Product 1

HCID 58714522(3Ez,5s)-5-{5-[(1s,2r)-1-amino-2-hydroxypropyl]-1,2,4-oxadiazol-3-yl}-1-([1,1'-biphenyl]-4-ylcarbonyl)-3-pyrrolidinone o-methyloximeYield 30%

Procedure

4-{[(2S,4EZ)-2-(5-{(1S,2R)-2-tert-butoxy-1-[(tert-butoxycarbonyl)amino]propyl}-1,2,4-oxadiazol-3-yl)-4-(methoxyimino)pyrrolidinyl]carbonyl}-1,1′-biphenyl (100 mg, 1.80 mmol) was treated with a 25% TFA/DCM solution at 0° C. for 1 hour. The reaction was then made basic with a sodium carbonate solution (10%) and extracted with DCM. The organic phases were combined and dried over magnesium sulfate and solvent removal afforded a residue, which was purified by flash-chromatography using dichloromethane/methanol as eluent to give the desired product, (3EZ,5S)-5-{5-[(1S,2R)-1-amino-2-hydroxypropyl]-1,2,4-oxadiazol-3-yl}-1-([1,1′-biphenyl]-4-ylcarbonyl)-3-pyrrolidinone O-methyloxime, as a mixture of E-/Z-isomers in 30% yield (90.3% purity by HPLC).

Workup

  1. extractionextracted with DCM
  2. dry with materialdried over magnesium sulfate and solvent removal
  3. customafforded a residue, which
  4. customwas purified by flash-chromatography

Sources & evidence

ORD record
ord-bd3079a9ea2c4140bf39621d3a1c42ec
Source dataset
uspto-grants-2006_10
Patent number
US07115639B2

Reaction notes

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