Water → HCID 58017101, compound

HRID 883649Notes

Reaction equation

HRID 883649 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.[C:27]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])(=[O:30])[CH:28]=[CH2:29].O>O1CCCC1>[C:32]([O:31][C:27](=[O:30])[CH2:28][CH2:29][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])([CH3:35])([CH3:34])[CH3:33]

Participants

6

Reactant 4

HCID 962WaterHCID 15458tert-Butyl acrylateHCID 24758Sodium hydrideHCID 24829235HCID 24829235, compound

Product 1

HCID 58017101HCID 58017101, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A stirred suspension of sodium hydride (60% dispersion in oil, 7 mg, 0.16 mmol) in anhydrous tetrahydrofuran (2 ml) was treated with 1′-benzyl-5-chloro-1H-spiro[indole-3,3′-pyrrolidine]-2,2′,5′-trione, intermediate 14 (50 mg, 0.15 mmol). After stirring at ambient temperature for 30 minutes, tert-butyl acrylate (0.03 ml, 0.19 mmol) was added and the resultant mixture stirred for 2 hours and left to stand at ambient temperature for 18 hours. Water (15 ml) was added and the mixture extracted with ethyl acetate (3×15 ml). The combined extracts were washed with brine (15 ml), dried (MgSO4) and the solvent removed in vacuo to give the crude 3-(1′-Benzyl-5-chloro-2,2′,5′-trioxo-spiro[indole-3,3′-pyrrolidin]-1-yl)-propionic acid tert-butyl ester. This was purified by flash chromatography (silica) eluting with petroleum ether (40-60) containing an increasing amount (0 to 50%) of ethyl acetate to give a white solid (37 mg 54%). This was sufficiently pure by 1H NMR to take on to the final hydrolysis step.

Workup

  1. waitleft
  2. waitto stand at ambient temperature for 18 hours
  3. extractionthe mixture extracted with ethyl acetate (3×15 ml)
  4. washThe combined extracts were washed with brine (15 ml)
  5. dry with materialdried (MgSO4)
  6. customthe solvent removed in vacuo

Sources & evidence

ORD record
ord-ead348113770492baa9bf6696d868947
Source dataset
uspto-grants-2012_08
Patent number
US08236963B2

Reaction notes

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