Aniline → 4-Anilino-1-benzylpiperidine-4-carbonitrile

HRID 507864Notes

Reaction equation

HRID 507864 reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][C:11](=O)[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:15]1([NH2:21])[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.[C-:22]#[N:23].[K+].[OH-].[NH4+]>C(O)(=O)C.O>[CH2:1]([N:8]1[CH2:13][CH2:12][C:11]([NH:21][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)([C:22]#[N:23])[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 6115AnilineHCID 9032Potassium CyanideHCID 14923Ammonium HydroxideHCID 192201-Benzyl-4-piperidone

Product 1

HCID 704124-Anilino-1-benzylpiperidine-4-carbonitrileYield 73.1%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 962WaterSolvent

Conditions

Temperature
25 °C

Procedure

To a solution of 1-benzyl-4-oxo-piperidine (226.8 g, 1.2 mol) and phenylamine (111.6 g, 1.2 mol) in acetic acid (1000 mL) was added dropwise the solution of potassium cyanide (117 g, 1.8 mol) in water (200 mL). The reaction mixture was stirred at 25° C. for 24 h and then poured into ice-water. The mixture was basified with ammonium hydroxide and extracted with CH2Cl2. The combined organic layers were washed with brine, dried over Na2SO4 and concentrated under reduced pressure to give crude benzyl-4-phenylamino-piperidine-4-carbonitrile (255.36 g, 73.1%), which was used directly in the next step. 1H NMR (300 MHz, CDCl3) δ 7.22-7.36 (m, 7H), 6.90-6.94 (m, 3H), 3.65 (br s, 1H), 3.58 (s, 2H), 2.74-2.86 (m, 2H), 2.44-2.52 (m, 2H), 2.32-2.37 (m, 2H), 1.92-2.00 (m, 2H).

Workup

  1. extractionextracted with CH2Cl2
  2. washThe combined organic layers were washed with brine
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-3810e7aa14234b0b87a6865d4c2b46f1
Source dataset
uspto-grants-2010_08
Patent number
US07786308B2

Reaction notes

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