2-Iodoxybenzoic acid → (2R)-1-benzyl-N-(4-(ethoxyamino)-3,4-dioxo-1-phenylbutan-2-yl)-5-oxopyrrolidine-2-carboxamide

HRID 2170892Notes

Reaction equation

HRID 2170892 reaction equation
I(C1C=CC=CC=1C(O)=O)(=O)=O.[CH2:13]([N:20]1[C:24](=[O:25])[CH2:23][CH2:22][C@@H:21]1[C:26]([NH:28][CH:29]([CH:37]([OH:44])[C:38]([NH:40][O:41][CH2:42][CH3:43])=[O:39])[CH2:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)=[O:27])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.C([O-])(O)=O.[Na+]>CS(C)=O.O.ClCCl>[CH2:13]([N:20]1[C:24](=[O:25])[CH2:23][CH2:22][C@@H:21]1[C:26]([NH:28][CH:29]([C:37](=[O:44])[C:38]([NH:40][O:41][CH2:42][CH3:43])=[O:39])[CH2:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)=[O:27])[C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1

Participants

7

Reactant 3

HCID 1087942-Iodoxybenzoic acid2×HCID 516892Sodium BicarbonateHCID 86652462(2R)-1-benzyl-N-(4-(ethoxyamino)-3-hydroxy-4-oxo-1-phenylbutan-2-yl)-5-oxopyrrolidine-2-carboxamide

Product 1

HCID 53257548(2R)-1-benzyl-N-(4-(ethoxyamino)-3,4-dioxo-1-phenylbutan-2-yl)-5-oxopyrrolidine-2-carboxamideYield 3.02%

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

IBX (2-iodoxybenzoic acid 432 mg, 0.694 mmol) was added to a solution of (2R)-1-benzyl-N-(4-(ethoxyamino)-3-hydroxy-4-oxo-1-phenylbutan-2-yl)-5-oxopyrrolidine-2-carboxamide (218 mg, 0.496 mmol) in DMSO (2 ml). After stiffing for 2 h at room temperature more IBX (123 mg, 0.198 mmol) was added and the stiffing was continued overnight. Saturated aqueous NaHCO3 solution was added and the reaction mixture was diluted with water and dichloromethane. The precipitate formed was filtered off, the organic layer was separated and the aqueous layer extracted with dichloromethane. The combined organic layers were washed with water and dried (MgSO4). The solvent was removed in vacuo, the resulting residue was redissolved in a small amount of dichloromethane and diethylether was added. The white precipitate formed was filtered, washed with diethylether and dried in vacuo. The crude product was dissolved in dichloromethane and treated with three drops of aqueous HCl (4M in dioxane). Removal of the solvent provided the title compound (8.2 mg, 0.015 mmol, 3.02% yield). ESI-MS [M+H]+=438.2

Workup

  1. waitthe stiffing was continued overnight
  2. customThe precipitate formed
  3. filtrationwas filtered off
  4. customthe organic layer was separated
  5. extractionthe aqueous layer extracted with dichloromethane
  6. washThe combined organic layers were washed with water
  7. dry with materialdried (MgSO4)
  8. customThe solvent was removed in vacuo
  9. dissolutionthe resulting residue was redissolved in a small amount of dichloromethane and diethylether
  10. additionwas added
  11. customThe white precipitate formed
  12. filtrationwas filtered
  13. washwashed with diethylether
  14. customdried in vacuo
  15. dissolutionThe crude product was dissolved in dichloromethane
  16. additiontreated with three drops of aqueous HCl (4M in dioxane)
  17. customRemoval of the solvent

Sources & evidence

ORD record
ord-8aab00a556d0423e83b7f9b3385cab8c
Source dataset
uspto-grants-2015_06
Patent number
US09051304B2

Reaction notes

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