Dimethylformamide → 5-Benzyl-7-t-butoxycarbonylamino-4-oxo-7-methyl-5-azaspiro[2.4]heptane

HRID 1675193Notes

Reaction equation

HRID 1675193 reaction equation
CN(C)C=O.[C:6]([O:10][C:11]([NH:13][C:14]1([CH3:22])[C:18]2([CH2:20][CH2:19]2)[C:17](=[O:21])[NH:16][CH2:15]1)=[O:12])([CH3:9])([CH3:8])[CH3:7].[H-].[Na+].[CH2:25](Br)[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1>C(OCC)(=O)C>[CH2:25]([N:16]1[CH2:15][C:14]([NH:13][C:11]([O:10][C:6]([CH3:9])([CH3:7])[CH3:8])=[O:12])([CH3:22])[C:18]2([CH2:19][CH2:20]2)[C:17]1=[O:21])[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 7498Benzyl BromideHCID 24758Sodium hydrideHCID 577586467-t-Butoxycarbonylamino-4-oxo-7-methyl-5-azaspiro[2.4]heptane

Product 1

HCID 577586535-Benzyl-7-t-butoxycarbonylamino-4-oxo-7-methyl-5-azaspiro[2.4]heptaneYield 98%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

A dimethylformamide solution (65 mL) of 7-(tert-butoxycarbonylamino)-7-methyl-5-azaspiro[2.4]heptan-4-one (3.12 g, 12.97 mmol) was added sodium hydride (55%, mineral oil dispersion, 538 mg, 12.33 mmol) over 5 minutes under cooling with ice. This solution was stirred at the same temperature for 40 minutes. After that, to the solution was added benzyl bromide (1.851 mL, 15.56 mmol), and the mixture was stirred at room temperature for 1.5 hours. To this reaction mixture was added ethyl acetate (300 mL) to dilute the mixture, and the mixture was washed with water (100 mL, ×2) and saturated brine (100 mL). To the solution was added anhydrous sodium sulfate to dry the solution. The drying agent was removed by filtration, and then the solvent was removed under reduced pressure. Thus-obtained residue was purified with silica gel column chromatography (hexane/ethyl acetate in the ratio of and in the order of 9:1, 4:1, and 2:1) to obtain 4.20 g (12.71 mmol, 98%) of the target compound as a transparent and colorless gum-like solid.

Workup

  1. temperatureunder cooling with ice
  2. stirringthe mixture was stirred at room temperature for 1.5 hours
  3. additionto dilute the mixture
  4. washthe mixture was washed with water (100 mL, ×2) and saturated brine (100 mL)
  5. additionTo the solution was added anhydrous sodium sulfate
  6. customto dry the solution
  7. customThe drying agent was removed by filtration
  8. customthe solvent was removed under reduced pressure
  9. customThus-obtained residue was purified with silica gel column chromatography (hexane/ethyl acetate in the ratio of and in the order of 9:1, 4:1, and 2:1)

Sources & evidence

ORD record
ord-267ca06963b64328be3b7fae9ae3277d
Source dataset
uspto-grants-2011_08
Patent number
US08003666B2

Reaction notes

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