Hydrogen Peroxide → HCID 76741083, compound

HRID 417357Notes

Reaction equation

HRID 417357 reaction equation
[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])[C:33]=2[F:39])=[O:11])=[N:7][CH:8]=1)#[N:2].[OH:40]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])[C:33]=2[F:39])=[O:11])=[N:7][CH:8]=1)(=[O:40])[NH2:2]

Participants

5

Reactant 3

HCID 784Hydrogen PeroxideHCID 14798Sodium HydroxideHCID 76741120HCID 76741120, compound

Product 1

HCID 76741083HCID 76741083, compoundYield 42.8%

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 (5-cyano-pyridin-2-yl)-amide (12 mg, 0.02 mmol) prepared in Example 199 in DMSO (0.2 mL) at 0° C. was added an aqueous solution (30% Aldrich) of H2O2 (0.04 g, 0.3 mmol), then aqueous solution (1N) of NaOH (0.1 mL, 0.1 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 chromatography (50-100% EtOAc in dichloromethane) 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 (5-carbamoyl-pyridin-2-yl)-amide as a light yellow solid (Yield 5 mg, 40%)

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 (50-100% EtOAc in dichloromethane)

Sources & evidence

ORD record
ord-262391e073b8422083e21bdfb020ec8a
Source dataset
uspto-grants-2012_01
Patent number
US08088815B2

Reaction notes

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