Isopropanol → 1-Benzyl-4-(ethylamino)piperidine-4-carbonitrile

HRID 348001Notes

Reaction equation

HRID 348001 reaction equation
[CH2:1]1[C:6](=O)[CH2:5][CH2:4][N:3]([CH2:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH2:2]1.Cl.[CH2:16]([NH2:18])[CH3:17].[C-:19]#[N:20].[K+].C(O)(C)C>C(O)C.O>[CH2:8]([N:3]1[CH2:4][CH2:5][C:6]([NH:18][CH2:16][CH3:17])([C:19]#[N:20])[CH2:1][CH2:2]1)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1

Participants

7

Reactant 4

HCID 3776IsopropanolHCID 9032Potassium CyanideHCID 11198Ethylamine hydrochlorideHCID 192201-Benzyl-4-piperidone

Product 1

HCID 705581-Benzyl-4-(ethylamino)piperidine-4-carbonitrileYield 84.3%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent2×

Procedure

To a solution of 4-N-benzylpiperidone (5.69 g, 29.5 mmol) in ethanol (4.2 ml) cooled in an ice bath was added ethylamine hydrochloride (2.69 g, 32.3 mmol) in water (3 ml), keeping the internal temperature of the reaction below 10° C. A solution of KCN (2.04 g, 31.3 mmol) in water (7 ml) was added to the reaction solution over 10 minutes while keeping the internal temperature below 10° C. The reaction was then warmed to room temperature and stirred 18 hours. Isopropanol (10 ml) was added to the reaction mixture to give two distinct layers: lower colorless aqueous layer and an orange organic upper layer. The organic layer was separated and stirred with water (30 ml) for 30 minutes. The organic layer was separated (orange organic layer now the bottom layer), the solvent was removed in vacuo, and the resultant oil diluted in methylene chloride (30 ml). The organic layer was washed with brine, dried (Na2SO4), filtered and concentrated, in vacuo, to give I-1A-1e as an orange oil (6.05 g, 84%): +APcI MS (M+1) 244.2; 1H NMR (400 MHz, CD2Cl2) δ 7.32 (d, J=4.1 Hz, 4H), 7.29–7.23 (m, 1H), 3.54 (s, 2H), 2.81–2.76 (m, 2H), 2.75 (q, J=7.1 Hz, 2H), 2.35–2.29 (m, 2H), 2.01–1.98 (m, 2H), 1.74–1.68 (m, 2H), 1.14 (t, J=7.1 Hz, 3H).

Workup

  1. customthe internal temperature of the reaction below 10° C
  2. customthe internal temperature below 10° C
  3. customto give two distinct layers
  4. customThe organic layer was separated
  5. stirringstirred with water (30 ml) for 30 minutes
  6. customThe organic layer was separated (orange organic layer now the bottom layer), the solvent
  7. customwas removed in vacuo
  8. additionthe resultant oil diluted in methylene chloride (30 ml)
  9. washThe organic layer was washed with brine
  10. dry with materialdried (Na2SO4)
  11. filtrationfiltered
  12. concentrationconcentrated, in vacuo

Sources & evidence

ORD record
ord-56baa37e9a684f02be65c99b0a02a23c
Source dataset
uspto-grants-2007_02
Patent number
US07176210B2

Reaction notes

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