Sodium hydride → (5-Chloro-2,2',5'-trioxo-spiro[indole-3,3'-pyrrolidin]-1-yl)acetic acid tert-butyl ester

HRID 883647Notes

Reaction equation

HRID 883647 reaction equation
[H-].[Na+].[Cl:3][C:4]1[CH:5]=[C:6]2[C:12]3([CH2:16][C:15](=[O:17])[NH:14][C:13]3=[O:18])[C:11](=[O:19])[NH:10][C:7]2=[CH:8][CH:9]=1.Br[CH2:21][C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23]>CN(C)C=O.[Cl-].[NH4+]>[C:25]([O:24][C:22](=[O:23])[CH2:21][N:10]1[C:7]2[C:6](=[CH:5][C:4]([Cl:3])=[CH:9][CH:8]=2)[C:12]2([CH2:16][C:15](=[O:17])[NH:14][C:13]2=[O:18])[C:11]1=[O:19])([CH3:28])([CH3:27])[CH3:26]

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 79177tert-Butyl bromoacetateHCID 20279349HCID 20279349, compound

Product 1

HCID 24828583(5-Chloro-2,2',5'-trioxo-spiro[indole-3,3'-pyrrolidin]-1-yl)acetic acid tert-butyl ester

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 25517Ammonium ChlorideSolvent

Procedure

A stirred suspension of sodium hydride (60% dispersion in mineral oil, 1.68 g, 42 mmol) in anhydrous N,N-dimethylformamide (140 ml) was treated with the crude 5-chloro-1H-spiro[indole-3,3′-pyrrolidine]-2,2′,5′-trione, intermediate 9 (5.0 g, 19.96 mmol). After stirring at ambient temperature for 40 min, the dark orange solution was cooled in an ice-bath and treated, over 30 min., with a solution of t-butyl bromoacetate (3.24 g, 2.26 ml, 18.96 mmol) in anhydrous N,N-dimethylformamide (46 ml). The resultant dark yellow mixture was allowed to come to ambient temperature and stirred for 4 hours. The resultant mixture was diluted with saturated aqueous ammonium chloride (500 ml) and extracted with ethyl acetate (3×200 ml). The combined extracts were dried (MgSO4) and the solvent removed to give the crude (5-Chloro-2,2′,5′-trioxo-spiro[indole-3,3′-pyrrolidin]-1-yl)acetic acid tert-butyl ester which was purified by flash chromatography (silica) eluting with petroleum ether (40-60) containing an increasing amount (0 to 80%) of ethyl acetate. This gave 4.76 g (95%) of a yellow solid.

Workup

  1. temperaturethe dark orange solution was cooled in an ice-bath
  2. customto come to ambient temperature
  3. stirringstirred for 4 hours
  4. extractionextracted with ethyl acetate (3×200 ml)
  5. dry with materialThe combined extracts were dried (MgSO4)
  6. customthe solvent removed

Sources & evidence

ORD record
ord-e3b0c9e9ab5a4bb0a75aae45a83f61b9
Source dataset
uspto-grants-2012_08
Patent number
US08236963B2

Reaction notes

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