Acetic Acid → Racemic 6-chloro-3-(3,3-dimethyl-1-nitromethyl-butyl)-1,3-dihydro-indol-2-one

HRID 2065391Notes

Reaction equation

HRID 2065391 reaction equation
[N+:1]([CH3:4])([O-:3])=[O:2].C[O-].[Na+].[Cl:8][C:9]1[CH:17]=[C:16]2[C:12](/[C:13](=[CH:19]/[CH2:20][C:21]([CH3:24])([CH3:23])[CH3:22])/[C:14](=[O:18])[NH:15]2)=[CH:11][CH:10]=1.C(O)(=O)C>CO>[Cl:8][C:9]1[CH:17]=[C:16]2[C:12]([CH:13]([CH:19]([CH2:4][N+:1]([O-:3])=[O:2])[CH2:20][C:21]([CH3:24])([CH3:23])[CH3:22])[C:14](=[O:18])[NH:15]2)=[CH:11][CH:10]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 6375NitromethaneHCID 10942334Sodium MethoxideHCID 86615083Z-6-chloro-3-(3,3-dimethyl-butylidene)-1,3-dihydro-indol-2-one

Product 1

HCID 58398993Racemic 6-chloro-3-(3,3-dimethyl-1-nitromethyl-butyl)-1,3-dihydro-indol-2-oneYield 90%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

To a solution of nitromethane (Aldrich) (1.7 g, 27 mmol) in methanol (20 mL) was slowly added a methanolic solution (Aldrich, 25 wt. %) of sodium methoxide (5.9 g, 27 mmol). After the mixture was stirred at room temperature for 10 min, a solution of E/Z-6-chloro-3-(3,3-dimethyl-butylidene)-1,3-dihydro-indol-2-one (3.4 g, 14 mmol) in methanol (20 mL) was added. The reaction mixture was stirred at room temperature for 2 h, then acetic acid (2.5 g, 41 mmol) was added. The mixture was concentrated to a small volume, then the residue was partitioned between ethyl acetate and water. The organic layer was separated, the aqueous layer was extracted with ethyl acetate. The organic layers were combined, washed with saturated aqueous NaHCO3, brine, dried over MgSO4, and concentrated. The residue was purified by chromatography (EtOAc:hexanes=1:5, 1:3) to give the racemic 6-chloro-3-(3,3-dimethyl-1-nitromethyl-butyl)-1,3-dihydro-indol-2-one as a white foam (3.8 g, 90%).

Workup

  1. stirringThe reaction mixture was stirred at room temperature for 2 h
  2. concentrationThe mixture was concentrated to a small volume
  3. customthe residue was partitioned between ethyl acetate and water
  4. customThe organic layer was separated
  5. extractionthe aqueous layer was extracted with ethyl acetate
  6. washwashed with saturated aqueous NaHCO3, brine
  7. dry with materialdried over MgSO4
  8. concentrationconcentrated
  9. customThe residue was purified by chromatography (EtOAc:hexanes=1:5, 1:3)

Sources & evidence

ORD record
ord-372a312fd5724a9f9fbcfe4cf12ea632
Source dataset
uspto-grants-2012_10
Patent number
US08288431B2

Reaction notes

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