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

HRID 417213Notes

Reaction equation

HRID 417213 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])[C:33]=2[F:39])=[O:11])=[C:5]([F:40])[CH:4]=1)#[N:2].[OH:41]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]=[CH:36][CH:35]=[C:34]([Cl:38])[C:33]=2[F:39])=[O:11])=[C:5]([F:40])[CH:4]=1)(=[O:41])[NH2:2]

Participants

5

Reactant 3

HCID 784Hydrogen PeroxideHCID 14798Sodium HydroxideHCID 75986020rac-(2'S,3'R,4'S,5'R)-6-chloro-4'-(3-chloro-2-fluoro-phenyl)-2'-(2,2-dimethyl-propyl)-2-oxo-1,2-dihydro-spiro[indole-3,3'-pyrrolidine]-5'-carboxylic acid (4-cyano-2-fluoro-phenyl)-amide

Product 1

HCID 75986021rac-(2'S,3'R,4'S,5'R)-6-chloro-4'-(3-chloro-2-fluoro-phenyl)-2'-(2,2-dimethyl-propyl)-2-oxo-1,2-dihydro-spiro[indole-3,3'-pyrrolidine]-5'-carboxylic acid (4-carbamoyl-2-fluoro-phenyl)-amide

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
0 °C

Procedure

To the solution of rac-(2′S,3′R,4′S,5′R)-6-chloro-4′-(3-chloro-2-fluoro-phenyl)-2′-(2,2-dimethyl-propyl)-2-oxo-1,2-dihydro-spiro[indole-3,3′-pyrrolidine]-5′-carboxylic acid (4-cyano-2-fluoro-phenyl)-amide (50 mg, 0.086 mmol) in DMSO (1 mL) at 0° C. was added an aqueous solution (30% Aldrich) of H2O2 (0.15 g, 1.3 mmol), then aqueous solution (1N) of NaOH (0.4 mL, 0.4 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 to give rac-(2′S,3′R,4′S,5′R)-6-chloro-4′-(3-chloro-2-fluoro-phenyl)-2′-(2,2-dimethyl-propyl)-2-oxo-1,2-dihydro-spiro[indole-3,3′-pyrrolidine]-5′-carboxylic acid (4-carbamoyl-2-fluoro-phenyl)-amide as a off white solid (Yield 25 mg, 49%)

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-d32e628040594912915de13da7cb80d4
Source dataset
uspto-grants-2012_01
Patent number
US08088815B2

Reaction notes

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