Water → HCID 90449655, compound

HRID 1411313Notes

Reaction equation

HRID 1411313 reaction equation
[H-].[Na+].[C:3]([O:11][CH2:12][CH3:13])(=[O:10])[CH2:4][C:5]([O:7][CH2:8][CH3:9])=[O:6].Br[CH2:15][CH:16]([CH2:47]Br)[CH2:17][C:18]1[CH:19]=[C:20]2[C:26]3([CH2:30][CH2:29][N:28]([C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[CH2:27]3)[CH2:25][N:24]([C:38]([O:40][CH2:41][CH2:42][Si:43]([CH3:46])([CH3:45])[CH3:44])=[O:39])[C:21]2=[CH:22][CH:23]=1.O>CN(C)C=O>[CH2:12]([O:11][C:3]([C:4]1([C:5]([O:7][CH2:8][CH3:9])=[O:6])[CH2:15][CH:16]([CH2:17][C:18]2[CH:19]=[C:20]3[C:26]4([CH2:30][CH2:29][N:28]([C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[CH2:27]4)[CH2:25][N:24]([C:38]([O:40][CH2:41][CH2:42][Si:43]([CH3:45])([CH3:46])[CH3:44])=[O:39])[C:21]3=[CH:22][CH:23]=2)[CH2:47]1)=[O:10])[CH3:13]

Participants

6

Reactant 4

HCID 962WaterHCID 7761Diethyl MalonateHCID 24758Sodium hydrideHCID 90449442HCID 90449442, compound

Product 1

HCID 90449655HCID 90449655, compoundYield 41.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
100 °C

Procedure

Sodium hydride (10.0 mg, 0.21 mmol) was dissolved in N,N-dimethylformamide (1 mL). Thereafter, diethyl malonate (13.0 μL, 0.086 mmol) was added to the above obtained solution under cooling on ice, and the thus obtained mixture was then stirred at 100° C. for 30 minutes. Thereafter, an N,N-dimethylformamide (0.5 mL) solution of 1-(2-(trimethylsilyl)ethyl) 1′-tert-butyl 5-(3-bromo-2-(bromomethyl)propyl)spiro[indoline-3,3′-pyrrolidine]-1,1′-dicarboxylate (51.1 mg, 0.080 mmol) was further added to the reaction solution under cooling on ice, and the thus obtained mixture was then stirred at 100° C. for 2 hours. Thereafter, water was added to the reaction solution, and the mixed solution was then extracted with ethyl acetate. The organic layer was washed with brine, and was then dried over anhydrous sodium sulfate, followed by concentration in vacuo. The obtained residue was purified by silica gel column chromatography (hexane ethyl acetate=5:1) to obtain 1-(2-(trimethylsilyl)ethyl) 1′-tert-butyl 5-((3,3-bis(ethoxycarbonyl)cyclobutyl)methyl)spiro[indoline-3,3′-pyrrolidine]-1,1′-dicarboxylate (20.8 mg, 41%) in the form of a colorless oily product.

Workup

  1. temperatureunder cooling on ice
  2. temperatureunder cooling on ice
  3. stirringthe thus obtained mixture was then stirred at 100° C. for 2 hours
  4. extractionthe mixed solution was then extracted with ethyl acetate
  5. washThe organic layer was washed with brine
  6. dry with materialwas then dried over anhydrous sodium sulfate
  7. concentrationfollowed by concentration in vacuo
  8. customThe obtained residue was purified by silica gel column chromatography (hexane ethyl acetate=5:1)

Sources & evidence

ORD record
ord-4e28e183cbdc4cd281fb59ac2d053486
Source dataset
uspto-grants-2014_12
Patent number
US08921576B2

Reaction notes

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