Water → HCID 24776290, compound

HRID 883650Notes

Reaction equation

HRID 883650 reaction equation
[H-].[Na+].[CH2:3]([N:10]1[C:14](=[O:15])[CH2:13][C:12]2([C:23]3[C:18](=[CH:19][CH:20]=[C:21]([Cl:24])[CH:22]=3)[NH:17][C:16]2=[O:25])[C:11]1=[O:26])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.Br[CH2:28][C:29]([O:31][CH2:32][CH3:33])=[O:30].O>O1CCCC1>[CH2:32]([O:31][C:29](=[O:30])[CH2:28][N:17]1[C:18]2[C:23](=[CH:22][C:21]([Cl:24])=[CH:20][CH:19]=2)[C:12]2([CH2:13][C:14](=[O:15])[N:10]([CH2:3][C:4]3[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=3)[C:11]2=[O:26])[C:16]1=[O:25])[CH3:33]

Participants

6

Reactant 4

HCID 962WaterHCID 7748Ethyl bromoacetateHCID 24758Sodium hydrideHCID 24829235HCID 24829235, compound

Product 1

HCID 24776290HCID 24776290, compoundYield 70%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A stirred suspension of sodium hydride (60% dispersion in oil [39 mg, 0.969 mmol]) in anhydrous tetrahydrofuran (10 ml) was treated with 1′-benzyl-5-chloro-1H-spiro[indole-3,3′-pyrrolidine]-2,2′,5′-trione, intermediate 14 (300 mg, 0.88 mmol). After stirring at ambient temperature for 30 min, the clear solution was treated with ethyl bromoacetate (0.13 ml, 1.16 mmol). The resultant suspension was stirred for 3 hours and then left to stand overnight. Water (50 ml) was added and the mixture extracted with ethyl acetate (3×50 ml). The combined extracts were washed with brine (50 ml), dried (MgSO4) and the solvent removed in vacuo to give the crude (1′-benzyl-5-chloro-2,2′,5′-trioxo-spiro[indole-3,3′-pyrrolidin]-1-yl)-acetic acid ethyl ester. Purification by flash chromatography (silica) eluting with petroleum ether (40-60) containing an increasing amount (0 to 50%) of ethyl acetate, followed by trituration with di-isopropyl ether gave a white solid (264 mg, 70%), m.pt. 143-144° C.

Workup

  1. waitleft
  2. waitto stand overnight
  3. extractionthe mixture extracted with ethyl acetate (3×50 ml)
  4. washThe combined extracts were washed with brine (50 ml)
  5. dry with materialdried (MgSO4)
  6. customthe solvent removed in vacuo
  7. customto give the crude (1′-benzyl-5-chloro-2,2′,5′-trioxo-spiro[indole-3,3′-pyrrolidin]-1-yl)-acetic acid ethyl ester
  8. customPurification by flash chromatography (silica)
  9. washeluting with petroleum ether (40-60)
  10. additioncontaining an increasing amount (0 to 50%) of ethyl acetate

Sources & evidence

ORD record
ord-223d7fbaaa634698b226f50d36982375
Source dataset
uspto-grants-2012_08
Patent number
US08236963B2

Reaction notes

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