Water → 7-Amino-5-benzyl-4-oxo-7-methyl-5-azaspiro[2.4]heptane

HRID 2078377Notes

Reaction equation

HRID 2078377 reaction equation
C(OC([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)(C)(C)C.C(O[K])(C)(C)C.[CH2:24](Cl)[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.O>CC(N(C)C)=O>[NH2:8][C:9]1([CH3:17])[C:13]2([CH2:14][CH2:15]2)[C:12](=[O:16])[N:11]([CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[CH2:10]1

Participants

6

Reactant 4

HCID 962WaterHCID 7503Benzyl ChlorideHCID 577586467-t-Butoxycarbonylamino-4-oxo-7-methyl-5-azaspiro[2.4]heptaneHCID 178418922HCID 178418922, compound

Product 1

HCID 575873067-Amino-5-benzyl-4-oxo-7-methyl-5-azaspiro[2.4]heptaneYield 90.1%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

A suspension of 7-t-butoxycarbonylamino-4-oxo-7-methyl-5-azaspiro[2.4]heptane (10.0 g, 41.6 mmol) in dimethylacetamide (100 mL) was cooled with ice, and t-butoxy potassium (4.67 g, 1.0 eq.) and benzyl chloride (5.27 mL, 1.1 eq.) were added thereto. The reaction mixture was returned to room temperature, followed by stirring for 2 hours. Thereafter, water was added to the mixture, followed by extraction with toluene. The solvent of the extract was evaporated under reduced pressure, to thereby yield 5-benzyl-7-t-butoxycarbonylamino-4-oxo-7-methyl-5-azaspiro[2.4]heptane as a crude product. The crude product was dissolved in toluene (100 mL), and methanesulfonic acid (2.97 mL) was added to the solution, followed by stirring under reflux for 2 hours. The reaction mixture was cooled to room temperature. Water was added to the cooled mixture for extraction, and the formed organic layer was removed. Aqueous sodium hydroxide solution (5N) was added to the remaining aqueous layer so as to alkalify the layer, followed by extraction with toluene. The solvent of the extract was evaporated under reduced pressure, to thereby yield the title product as a pale brown solid (8.63 g, yield: 90.1%).

Workup

  1. additionwere added
  2. customwas returned to room temperature
  3. extractionfollowed by extraction with toluene
  4. customThe solvent of the extract was evaporated under reduced pressure
  5. dissolutionThe crude product was dissolved in toluene (100 mL)
  6. additionmethanesulfonic acid (2.97 mL) was added to the solution
  7. stirringby stirring
  8. temperatureunder reflux for 2 hours
  9. additionWater was added to the cooled mixture for extraction
  10. customthe formed organic layer was removed
  11. additionAqueous sodium hydroxide solution (5N) was added to the remaining aqueous layer so as
  12. extractionfollowed by extraction with toluene
  13. customThe solvent of the extract was evaporated under reduced pressure

Sources & evidence

ORD record
ord-33d955de0db44d74af56d53689a465f3
Source dataset
uspto-grants-2011_04
Patent number
US07928232B2

Reaction notes

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