Hydrogen Cyanide → 3-Methyl-1-phenyl-1,3,7-triaza-spiro[4.5]decan-4-one

HRID 1036714Notes

Reaction equation

HRID 1036714 reaction equation
C(O[C:6]([N:8]1[CH2:13][CH2:12][CH2:11][C:10](=O)[CH2:9]1)=O)(C)(C)C.[NH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.C[Si]([C:26]#[N:27])(C)C.[OH-:28].[NH4+].[CH:30]#N>C(O)(=O)C.CCOC(C)=O>[CH3:13][N:8]1[C:9](=[O:28])[C:10]2([CH2:11][CH2:12][CH2:26][NH:27][CH2:30]2)[N:15]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH2:6]1

Participants

8

Reactant 5

HCID 768Hydrogen CyanideHCID 6115AnilineHCID 14923Ammonium HydroxideHCID 82115Trimethylsilyl cyanideHCID 2756825Tert-butyl 3-oxopiperidine-1-carboxylate

Product 1

HCID 710602063-Methyl-1-phenyl-1,3,7-triaza-spiro[4.5]decan-4-one

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution comprising of 3-Oxo-piperidine-1-carboxylic acid tert-butyl ester (2.5 g, 12.55 mol) and aniline (1.28 g, 13.8 mmol) in acetic acid (10 ml) was stirred at RT for 60 mins under nitrogen. Trimethylsilyl cyanide (1.57 ml, 12.55 mmol) was added carefully into the reaction mixture. The reaction mixture was left to stir at RT for a further 90 mins. The reaction mixture was cannulated into a rapidly stirring flask containing crushed ice (50 ml) and concentrated ammonium hydroxide (30 ml) for 10 minutes, resulting in a precipitate. This solution was allowed to stir for a further 15 mins to ensure no HCN remained before adding EtOAc (150 ml) to dissolve the precipitate. The organics were then separated and the aqueous washed with a further EtOAc (50 ml). The organics portions were combined, washed with brine (100 ml), dried (MgSO4) and concentrated in vacuo to afford an oil. Purification of the crude product by chromatography on silica eluting with 0-50% EtOAc in iso-hexane afforded the title compound.

Workup

  1. waitThe reaction mixture was left
  2. stirringa rapidly stirring flask
  3. additioncontaining
  4. customresulting in a precipitate
  5. stirringto stir for a further 15 mins
  6. dissolutionto dissolve the precipitate
  7. customThe organics were then separated
  8. washthe aqueous washed with a further EtOAc (50 ml)
  9. washwashed with brine (100 ml)
  10. dry with materialdried (MgSO4)
  11. concentrationconcentrated in vacuo
  12. customto afford an oil
  13. customPurification of the crude product by chromatography on silica eluting with 0-50% EtOAc in iso-hexane

Sources & evidence

ORD record
ord-8d0c34f92c464e5ebd97d6499c077d0f
Source dataset
uspto-grants-2013_10
Patent number
US08546416B2

Reaction notes

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