2-(tert-Butoxycarbonyloxyimino)-2-phenylacetonitrile → 7-Tert-butoxycarbonylamino-5-benzyl-5-azaspiro[2,4]heptane

HRID 1721092Notes

Reaction equation

HRID 1721092 reaction equation
[NH2:1][CH:2]1[C:6]2([CH2:8][CH2:7]2)[CH2:5][N:4]([CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH2:3]1.[C:16]([O:20][C:21](ON=C(C1C=CC=CC=1)C#N)=[O:22])([CH3:19])([CH3:18])[CH3:17]>O1CCCC1>[C:16]([O:20][C:21]([NH:1][CH:2]1[C:6]2([CH2:8][CH2:7]2)[CH2:5][N:4]([CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH2:3]1)=[O:22])([CH3:19])([CH3:18])[CH3:17]

Participants

4

Reactant 2

HCID 938652-(tert-Butoxycarbonyloxyimino)-2-phenylacetonitrileHCID 108565665-Benzyl-5-azaspiro[2.4]heptan-7-amine

Product 1

HCID 224171627-Tert-butoxycarbonylamino-5-benzyl-5-azaspiro[2,4]heptaneYield 75.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

In 30 ml of tetrahydrofuran was dissolved 800 mg of compound 6 followed by the addition of 1.2 g of 2-(tert-butoxycarbonyloxyimino)-2-phenylacetonitrile (BOC-ON) at room temperature and the mixture was stirred at that temperature for 2 hours. The solvent was then removed under reduced pressure and to the residue was added chloroform. The mixture was extracted with a 10% aqueous citric acid. The citric acid extract was adjusted to pH≥10 with 1N aqueous sodium hydroxide and extracted with chloroform. The extract was dried over anhydrous sodium sulfate and the solvent was removed under reduced pressure to give 900 mg of 7-tert-butoxycarbonylamino-5-benzyl-5-azaspiro[2.4]heptane (compound 10). 870 mg of this compound 10 was dissolved in 15 ml of ethanol and catalytic hydrogenation was carried out at 40° C. and 4.5 kg/cm2 in the presence of 500 mg of 10% palladium-on-carbon for 2 hours. The catalyst was then filtered off and the filtrate was concentrated under reduced pressure to give title compound 11. This product was used without purification in the substitution reaction.

Workup

  1. customThe solvent was then removed under reduced pressure and to the residue
  2. additionwas added chloroform
  3. extractionThe mixture was extracted with a 10% aqueous citric acid
  4. extractionThe citric acid extract
  5. extractionextracted with chloroform
  6. dry with materialThe extract was dried over anhydrous sodium sulfate
  7. customthe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-de067a86d7ce4b499dcc0f107da146f7
Source dataset
uspto-grants-1996_04
Patent number
US05508428

Reaction notes

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