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

HRID 229511Notes

Reaction equation

HRID 229511 reaction equation
[C:1]([O:5][C:6]([NH:8][C:9]1([CH3:17])[C:13]2([CH2:15][CH2:14]2)[C:12](=[O:16])[NH:11][CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[CH2:20](Br)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.C(OCC)(=O)C>CN(C)C=O>[CH2:20]([N:11]1[CH2:10][C:9]([NH:8][C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])([CH3:17])[C:13]2([CH2:14][CH2:15]2)[C:12]1=[O:16])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1

Participants

6

Reactant 4

HCID 7498Benzyl BromideHCID 8857Ethyl AcetateHCID 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 6228DimethylformamideSolvent

Procedure

To a solution (65 mL) of 7-(tert-butoxycarbonylamino)-7-methyl-5-azaspiro[2.4]heptan-4-one (3.12 g, 12.97 mmol) in dimethylformamide in an ice bath was gradually added sodium hydride (55%, dispersion in a mineral oil, 538 mg, 12.33 mmol) in 5 minutes, and the mixture was stirred at the same temperature for 40 minutes. Benzyl bromide (1.851 mL, 15.56 mmol) was added, and the mixture was stirred at room temperature for 1.5 hours. The reaction mixture was diluted by adding ethyl acetate (300 mL), and the solution was washed with water (100 mL×2) and saturated aqueous solution of sodium chloride (100 mL). After drying the solution with anhydrous sodium sulfate and removing the dessicating agent by filtration, the solvent was removed by distillation under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate, 9:1→4:1→2:1) to obtain 4.20 g (12.71 mmol, 98%) of the target compound as a colorless transparent gummy solid.

Workup

  1. stirringthe mixture was stirred at room temperature for 1.5 hours
  2. additionThe reaction mixture was diluted
  3. washthe solution was washed with water (100 mL×2) and saturated aqueous solution of sodium chloride (100 mL)
  4. dry with materialAfter drying the solution with anhydrous sodium sulfate
  5. customremoving the dessicating agent
  6. filtrationby filtration
  7. customthe solvent was removed by distillation under reduced pressure
  8. customThe residue was purified by silica gel column chromatography (hexane:ethyl acetate, 9:1→4:1→2:1)

Sources & evidence

ORD record
ord-8743126d0bcd40959feae14f95bd16b6
Source dataset
uspto-grants-2009_07
Patent number
US07563805B2

Reaction notes

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