Hydrochloric Acid → Ethyl 2-cyano-1-imino-8-azaspiro[4,5]decane-8-carboxylate hemihydrate

HRID 1017547Notes

Reaction equation

HRID 1017547 reaction equation
[C:1]([CH2:3][CH2:4][CH2:5][C:6]1([C:17]#[N:18])[CH2:11][CH2:10][N:9]([C:12]([O:14][CH2:15][CH3:16])=[O:13])[CH2:8][CH2:7]1)#[N:2].C([N-]C(C)C)(C)C.[Li+].Cl>O1CCCC1>[OH2:13].[C:1]([CH:3]1[CH2:4][CH2:5][C:6]2([CH2:11][CH2:10][N:9]([C:12]([O:14][CH2:15][CH3:16])=[O:13])[CH2:8][CH2:7]2)[C:17]1=[NH:18])#[N:2].[CH2:15]([O:14][C:12]([N:9]1[CH2:10][CH2:11][C:6]2([C:17](=[NH:18])[CH:3]([C:1]#[N:2])[CH2:4][CH2:5]2)[CH2:7][CH2:8]1)=[O:13])[CH3:16]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 2724682Lithium diisopropylamideHCID 10198845Ethyl 4-(3-cyanopropyl)-4-cyano-1-piperidinecarboxylate

Product 1

HCID 131720679Ethyl 2-cyano-1-imino-8-azaspiro[4,5]decane-8-carboxylate hemihydrateYield 52.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of ethyl 4-(3-cyanopropyl)4cyano- 1-piperidinecarboxylate (5 g) in tetrahydrofuran (75 ml) was added lithium diisopropylamide (2.5 g) at −70° C., under nitrogen, with stirring. The reaction mixture was warmed to ambient temperature over 10 min and heated at reflux for 90 min. The reaction mixture was cooled to ambient temperature, neutralized with 5% hydrochloric acid and extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, filtered, and the filtrate was concentrated in vacuo. The residue was recrystallized from chloroform/petroleum ether to afford 1.8 g (36%) of product, mp 215-216° C.

Workup

  1. temperatureheated
  2. temperatureat reflux for 90 min
  3. temperatureThe reaction mixture was cooled to ambient temperature
  4. extractionextracted with ethyl acetate
  5. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  6. filtrationfiltered
  7. concentrationthe filtrate was concentrated in vacuo
  8. customThe residue was recrystallized from chloroform/petroleum ether

Sources & evidence

ORD record
ord-526c14a85b5f4ae08bac99519f4879f3
Source dataset
uspto-grants-2002_11
Patent number
US06479501B2

Reaction notes

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