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

HRID 417269Notes

Reaction equation

HRID 417269 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]=[C:36]([F:38])[CH:35]=[C:34]([Cl:39])[CH:33]=2)=[O:11])=[C:5]([O:40][CH3:41])[CH:4]=1)#[N:2].[OH:42]O.[OH-].[Na+]>CS(C)=O>[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]=[C:36]([F:38])[CH:35]=[C:34]([Cl:39])[CH:33]=2)=[O:11])=[C:5]([O:40][CH3:41])[CH:4]=1)(=[O:42])[NH2:2]

Participants

5

Reactant 3

HCID 784Hydrogen PeroxideHCID 14798Sodium HydroxideHCID 75985333rac-(2'S,3'R,4'R,5'R)-6-chloro-4'-(3-chloro-5-fluoro-phenyl)-2'-(2,2-dimethyl-propyl)-2-oxo-1,2-dihydro-spiro[indole-3,3'-pyrrolidine]-5'-carboxylic acid (4-cyano-2-methoxy-phenyl)-amide

Product 1

HCID 75985334rac-(2'S,3'R,4'R,5'R)-6-chloro-4'-(3-chloro-5-fluoro-phenyl)-2'-(2,2-dimethyl-propyl)-2-oxo-1,2-dihydro-spiro[indole-3,3'-pyrrolidine]-5'-carboxylic acid (4-carbamoyl-2-methoxy-phenyl)-amideYield 105.9%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
10 °C

Procedure

To the solution of rac-(2′S,3′R,4′R,5′R)-6-chloro-4′-(3-chloro-5-fluoro-phenyl)-2′-(2,2-dimethyl-propyl)-2-oxo-1,2-dihydro-Spiro[indole-3,3′-pyrrolidine]-5′-carboxylic acid (4-cyano-2-methoxy-phenyl)-amide (0.14 g, 0.2 mmol) prepared in Example 114 in DMSO (1 mL) at 0° C. was added an aqueous solution (30% Aldrich) of H2O2 (0.4 g, 3.5 mmol), then aqueous solution (1N) of NaOH (1.2 mL, 1.2 mmol) was added dropwise. The reaction mixture was stirred at 10° 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 to give rac-(2′S,3′R,4′R,5′R)-6-chloro-4′-(3-chloro-5-fluoro-phenyl)-2′-(2,2-dimethyl-propyl)-2-oxo-1,2-dihydro-spiro[indole-3,3′-pyrrolidine]-5′-carboxylic acid (4-carbamoyl-2-methoxy-phenyl)-amide as a white solid (Yield 0.13 g, 87%)

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

Sources & evidence

ORD record
ord-f8eed6c581b2496eb8ec8a84e8ac78b3
Source dataset
uspto-grants-2012_01
Patent number
US08088815B2

Reaction notes

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