tert-butyl 1-((2S)-2-{[(benzyloxy)carbonyl]amino}-1-(tert-butyldimethylsilyloxy) butyl)cyclopropanecarboxylate → (6S)-7-(tert-butyldimethylsilyloxy)-6-ethyl-5-azaspiro[2.4]heptan-4-one

HRID 1967287Notes

Reaction equation

HRID 1967287 reaction equation
C(OC([NH:11][C@@H:12]([CH2:32][CH3:33])[CH:13]([C:22]1([C:25](OC(C)(C)C)=[O:26])[CH2:24][CH2:23]1)[O:14][Si:15]([C:18]([CH3:21])([CH3:20])[CH3:19])([CH3:17])[CH3:16])=O)C1C=CC=CC=1>CO.[C].[Pd]>[Si:15]([O:14][CH:13]1[C:22]2([CH2:24][CH2:23]2)[C:25](=[O:26])[NH:11][C@H:12]1[CH2:32][CH3:33])([C:18]([CH3:21])([CH3:20])[CH3:19])([CH3:17])[CH3:16]

Participants

4

Reactant 1

HCID 59556935tert-butyl 1-((2S)-2-{[(benzyloxy)carbonyl]amino}-1-(tert-butyldimethylsilyloxy) butyl)cyclopropanecarboxylate

Product 1

HCID 58238351(6S)-7-(tert-butyldimethylsilyloxy)-6-ethyl-5-azaspiro[2.4]heptan-4-oneYield 60%

Reagents, catalysts & solvents 2

HCID 178418390HCID 178418390, compoundCatalystHCID 887MethanolSolvent

Procedure

To a solution of tert-butyl 1-((2S)-2-{[(benzyloxy)carbonyl]amino}-1-(tert-butyldimethylsilyloxy)butyl)cyclopropanecarboxylate (1.18 g) in methanol (20 mL) was added 10% palladium carbon (150 mg), and the mixture was stirred at room temperature for 18 hr under a hydrogen atmosphere and filtered. The filtrate was concentrated under reduced pressure and the residue was dissolved in methanol (20 mL). Sodium methoxide (230 mg) was added and the mixture was refluxed for 2.5 hr. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane/ethyl acetate=30/1→1/2) to give the title compound as a colorless oil (yield: 397.8 mg, 60%).

Workup

  1. filtrationfiltered
  2. concentrationThe filtrate was concentrated under reduced pressure
  3. dissolutionthe residue was dissolved in methanol (20 mL)
  4. additionSodium methoxide (230 mg) was added
  5. temperaturethe mixture was refluxed for 2.5 hr
  6. additionWater was added to the reaction mixture
  7. extractionthe mixture was extracted with ethyl acetate
  8. dry with materialThe extract was dried over anhydrous magnesium sulfate
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was purified by silica gel column chromatography (eluent: hexane/ethyl acetate=30/1→1/2)

Sources & evidence

ORD record
ord-3b6494bd174646f18d41310ddaecc82b
Source dataset
uspto-grants-2013_04
Patent number
US08420694B2

Reaction notes

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