Hydrogen Peroxide → 2-Oxo-1,2-dihydro-spiro[indole-3,3'-pyrrolidine]-5'-carboxylic acid (4-carbamoyl-phenyl)-amide

HRID 417261Notes

Reaction equation

HRID 417261 reaction equation
Cl[C:2]1[CH:7]=[C:6]2[NH:8][C:9](=[O:43])[C@:10]3([C@@H:14](C4C=CC=C(Cl)C=4F)[C@H:13]([C:23](=[O:33])[NH:24][C:25]4[CH:30]=[CH:29][C:28]([C:31]#[N:32])=[CH:27][CH:26]=4)[NH:12][C@H:11]3CC(C)(C)COC(=O)C)[C:5]2=[CH:4][CH:3]=1.[OH:44]O.[OH-].[Na+]>CS(C)=O>[C:31]([C:28]1[CH:29]=[CH:30][C:25]([NH:24][C:23]([CH:13]2[NH:12][CH2:11][C:10]3([C:5]4[C:6](=[CH:7][CH:2]=[CH:3][CH:4]=4)[NH:8][C:9]3=[O:43])[CH2:14]2)=[O:33])=[CH:26][CH:27]=1)(=[O:44])[NH2:32]

Participants

5

Reactant 3

HCID 784Hydrogen PeroxideHCID 14798Sodium HydroxideHCID 53239123acetic acid rac-3-[(2'S,3'R,4'S,5'R)-6-chloro-4'-(3-chloro-2-fluoro-phenyl)-5'-(4-cyano-phenylcarbamoyl)-2-oxo-1,2-dihydro-spiro[indole-3,3'-pyrrolidin]-2'-yl]-2,2-dimethyl-propyl ester

Product 1

HCID 1236048552-Oxo-1,2-dihydro-spiro[indole-3,3'-pyrrolidine]-5'-carboxylic acid (4-carbamoyl-phenyl)-amideYield 160.3%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

To the solution of acetic acid rac-3-[(2′S,3′R,4′S,5′R)-6-chloro-4′-(3-chloro-2-fluoro-phenyl)-5′-(4-cyano-phenylcarbamoyl)-2-oxo-1,2-dihydro-spiro[indole-3,3′-pyrrolidin]-2′-yl]-2,2-dimethyl-propyl ester prepared in Example 104 (80 mg, 0.13 mmol) in DMSO (0.5 mL) at 0° C. was added an aqueous solution (30% Aldrich) of H2O2 (0.22 g, 1.9 mmol), then aqueous solution (1N) of NaOH (0.64 mL, 0.64 mmol) was added dropwise. The reaction mixture was stirred at room temperature for 5 h. The mixture was partitioned between ethyl acetate and saturated aqueous Na2SO3 solution. The organic layer was separated, washed with water, brine, dried over MgSO4, and concentrated. The residue was purified by chromatography (50 to 100% EtOAc in CH2Cl2) to give rac-(2′S,3′R,4′S,5′R)-6-chloro-4′-(3-chloro-2-fluoro-phenyl)-2′43-hydroxy-2,2-dimethyl-propyl)-2-oxo-1,2-dihydro-spiro[indole-3,3′-pyrrolidine]-5′-carboxylic acid (4-carbamoyl-phenyl)-amide as a white solid (Yield 73 mg, 95%)

Workup

  1. customThe mixture was partitioned between ethyl acetate and saturated aqueous Na2SO3 solution
  2. customThe organic layer was separated
  3. washwashed with water, brine
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated
  6. customThe residue was purified by chromatography (50 to 100% EtOAc in CH2Cl2)

Sources & evidence

ORD record
ord-f7747d3f5947432aab5ef575c385aceb
Source dataset
uspto-grants-2012_01
Patent number
US08088815B2

Reaction notes

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