Ceric ammonium nitrate → 1-((2R)-2-Cyclohexyl-2-hydroxyethanoyl)-N-(2-(1-amino-2,2-difluoroethyl)-5-chlorobenzyl)-L-prolinamide

HRID 1058238Notes

Reaction equation

HRID 1058238 reaction equation
O=[N+]([O-])[O-].[O-][N+](=O)[O-].[O-][N+](=O)[O-].[O-][N+](=O)[O-].[O-][N+](=O)[O-].[O-][N+](=O)[O-].[Ce+4].[NH4+].[NH4+].[Cl:28][C:29]1[CH:30]=[CH:31][C:32]([CH:54]([NH:58]C2C=CC(OC)=CC=2)[CH:55]([F:57])[F:56])=[C:33]([CH:53]=1)[CH2:34][NH:35][C:36](=[O:52])[C@@H:37]1[CH2:41][CH2:40][CH2:39][N:38]1[C:42](=[O:51])[C@@H:43]([CH:45]1[CH2:50][CH2:49][CH2:48][CH2:47][CH2:46]1)[OH:44]>O.CC#N>[CH:45]1([C@@H:43]([OH:44])[C:42]([N:38]2[CH2:39][CH2:40][CH2:41][C@H:37]2[C:36]([NH:35][CH2:34][C:33]2[CH:53]=[C:29]([Cl:28])[CH:30]=[CH:31][C:32]=2[CH:54]([NH2:58])[CH:55]([F:57])[F:56])=[O:52])=[O:51])[CH2:46][CH2:47][CH2:48][CH2:49][CH2:50]1

Participants

5

Reactant 2

HCID 180504Ceric ammonium nitrateHCID 69937977N-(5-chloro-2-{2,2-difluoro-1-[(4-methoxyphenyl)amino]ethyl}benzyl)-1-[(2R)-2-cyclohexyl-2-hydroxyethanoyl]-L-prolinamide

Product 1

HCID 590382151-((2R)-2-Cyclohexyl-2-hydroxyethanoyl)-N-(2-(1-amino-2,2-difluoroethyl)-5-chlorobenzyl)-L-prolinamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

A solution of CAN (0.0647 g, 0.12 mmol) in water (0.4 mL) was added to a stirred solution of N-(5-chloro-2-{2,2-difluoro-1-[(4-methoxyphenyl)amino]ethyl}benzyl)-1-[(2R)-2-cyclohexyl-2-hydroxyethanoyl]-L-prolinamide (0.0332 g, 0.06 mmol) in CH3CN (1.5 mL) at 0° C. and the solution was warmed to ambient temperature. After 4 h the solution was partitioned between EtOAc and 10% aqueous NH4OH. The resulting two phase suspension was filtered and the EtOAc layer was washed with 10% sodium sulfite solution and brine, dried (Na2SO4) and evaporated in vacuo. The residue was purified by column chromatography on silica (eluting with 1-10% of 10% ammonium hydroxide in methanol/chloroform gradient) to give the title compound as a gum: LC-MS m/z=458.4.

Workup

  1. customAfter 4 h the solution was partitioned between EtOAc and 10% aqueous NH4OH
  2. filtrationThe resulting two phase suspension was filtered
  3. washthe EtOAc layer was washed with 10% sodium sulfite solution and brine
  4. dry with materialdried (Na2SO4)
  5. customevaporated in vacuo
  6. customThe residue was purified by column chromatography on silica (eluting with 1-10% of 10% ammonium hydroxide in methanol/chloroform gradient)

Sources & evidence

ORD record
ord-29ca13c10d9b48778916236b16551a4b
Source dataset
uspto-grants-2003_02
Patent number
US06515011B2

Reaction notes

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