Triethylamine → Tert-butyl 2-oxo-1-oxa-3,8-diazaspiro[4.5]decane-8-carboxylate

HRID 1691652Notes

Reaction equation

HRID 1691652 reaction equation
C([N:3]([CH2:6]C)CC)C.C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:15])C=CC=CC=1.[C:25]([O:29][C:30]([N:32]1[CH2:37][CH2:36][C:35]([CH2:39]C(O)=O)([OH:38])[CH2:34][CH2:33]1)=[O:31])([CH3:28])([CH3:27])[CH3:26]>C1(C)C=CC=CC=1.CCOC(C)=O>[C:25]([O:29][C:30]([N:32]1[CH2:33][CH2:34][C:35]2([O:38][C:6](=[O:15])[NH:3][CH2:39]2)[CH2:36][CH2:37]1)=[O:31])([CH3:26])([CH3:27])[CH3:28]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 199401P,P-Diphenylphosphinic azideHCID 100611062-{1-[(Tert-butoxy)carbonyl]-4-hydroxypiperidin-4-yl}acetic acid

Product 1

HCID 10015278Tert-butyl 2-oxo-1-oxa-3,8-diazaspiro[4.5]decane-8-carboxylate

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
85 °C

Procedure

Triethylamine (5.59 mL, 39.78 mmol) and diphenylphosphoryl azide (10.86 mL, 5.1 mmol) were added in succession under a nitrogen atmosphere to a solution of A2 (7.9 g) in dry toluene (205 mL). The reaction mixture was heated to 80 to 90° C., evolution of gas being observed which ceased after 90 min. Stirring was continued for a further 2 h at 115° C. After cooling, the reaction mixture was diluted with EtOAc and repeatedly washed with water. The combined aqueous phases were extracted with EtOAc and the combined organic phases were washed with sat. aq. NaCl solution, dried over Na2SO4 and the solvent was removed under a vacuum. The residue was washed repeatedly with ether. 5.72 g (60.6% of theoretical over three stages starting from 1-(tert-butyloxycarbonyl)-4-piperidone) of the desired product 2-oxo-1-oxa-3,8-diazaspiro[4.5]decane-8-carboxylic acid tert-butyl ester (A3) remained as a white solid.

Workup

  1. waitwas continued for a further 2 h at 115° C
  2. temperatureAfter cooling
  3. washrepeatedly washed with water
  4. extractionThe combined aqueous phases were extracted with EtOAc
  5. washthe combined organic phases were washed with sat. aq. NaCl solution
  6. dry with materialdried over Na2SO4
  7. customthe solvent was removed under a vacuum
  8. washThe residue was washed repeatedly with ether

Sources & evidence

ORD record
ord-d078cea0592947dfacdf2274735f2730
Source dataset
uspto-grants-2012_04
Patent number
US08153795B2

Reaction notes

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