Hydrogen Peroxide → rac-(2'S,3'R,4'R,5'R)-6-chloro-4'-(3-chloro-phenyl)-2'-(2,2-dimethyl-propyl)-2-oxo-1,2-dihydro-spiro[indole-3,3'-pyrrolidine]-5'-carboxylic acid (4-carbamoyl-phenyl)-amide

HRID 417223Notes

Reaction equation

HRID 417223 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([NH:9][C:10]([CH:12]2[NH:16][CH:15]([CH2:17][C:18]([CH3:21])([CH3:20])[CH3:19])[C:14]3([C:29]4[C:24](=[CH:25][C:26]([Cl:30])=[CH:27][CH:28]=4)[NH:23][C:22]3=[O:31])[CH:13]2[C:32]2[CH:37]=[CH:36][CH:35]=[C:34]([Cl:38])[CH:33]=2)=[O:11])=[CH:5][CH:4]=1)#[N:2].[OH:39]O.[OH-].[Na+]>CS(C)=O>[C:1]([C:3]1[CH:4]=[CH:5][C:6]([NH:9][C:10]([CH:12]2[NH:16][CH:15]([CH2:17][C:18]([CH3:21])([CH3:20])[CH3:19])[C:14]3([C:29]4[C:24](=[CH:25][C:26]([Cl:30])=[CH:27][CH:28]=4)[NH:23][C:22]3=[O:31])[CH:13]2[C:32]2[CH:37]=[CH:36][CH:35]=[C:34]([Cl:38])[CH:33]=2)=[O:11])=[CH:7][CH:8]=1)(=[O:39])[NH2:2]

Participants

5

Reactant 3

HCID 784Hydrogen PeroxideHCID 14798Sodium HydroxideHCID 67227681rac-(2'S,3'R,4'R,5'R)-6-chloro-4'-(3-chloro-phenyl)-2'-(2,2-dimethyl-propyl)-2-oxo-1,2-dihydro-spiro[indole-3,3'-pyrrolidine]-5'-carboxylic acid (4-cyano-phenyl)-amide

Product 1

HCID 75986158rac-(2'S,3'R,4'R,5'R)-6-chloro-4'-(3-chloro-phenyl)-2'-(2,2-dimethyl-propyl)-2-oxo-1,2-dihydro-spiro[indole-3,3'-pyrrolidine]-5'-carboxylic acid (4-carbamoyl-phenyl)-amideYield 58.3%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
0 °C

Procedure

To the solution of rac-(2′S,3′R,4′R,5′R)-6-chloro-4′-(3-chloro-phenyl)-2′-(2,2-dimethyl-propyl)-2-oxo-1,2-dihydro-spiro[indole-3,3′-pyrrolidine]-5′-carboxylic acid (4-cyano-phenyl)-amide (0.5 g, 0.91 mmol) prepared in Example 64 in DMSO (15 mL) at 0° C. was added an aqueous solution (30% Aldrich) of H2O2 (0.56 mL, 18 mmol), then aqueous solution (1N) of NaOH (4 mL, 4 mmol) was added dropwise. The reaction mixture was stirred at 0° C. for 1 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 chromatograph (50-100% EtOAc in CH2Cl2) to give rac-(2′S,3′R,4′R,5′R)-6-chloro-4′-(3-chloro-phenyl)-2′-(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 0.3 g, 58%)

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 chromatograph (50-100% EtOAc in CH2Cl2)

Sources & evidence

ORD record
ord-a81b02545e6b4673abd79e5134fd1274
Source dataset
uspto-grants-2012_01
Patent number
US08088815B2

Reaction notes

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