Sodium Hydroxide → 4-amino-1-benzylpiperidine-4-carbonitrile

HRID 2365523Notes

Reaction equation

HRID 2365523 reaction equation
[H-].[Al+3].[Li+].[H-].[H-].[H-].[NH2:7][CH2:8][C:9]1([NH2:22])[CH2:14][CH2:13][N:12]([CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH2:11][CH2:10]1.[OH-].[Na+].[O-]S([O-])(=O)=O.[Mg+2]>C(OCC)C.O>[NH2:22][C:9]1([C:8]#[N:7])[CH2:14][CH2:13][N:12]([CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH2:11][CH2:10]1

Participants

7

Reactant 4

HCID 14798Sodium HydroxideHCID 24083Sulfuric acid magnesium salt (1:1)HCID 15965878HCID 15965878, compoundHCID 21226445Aluminium lithium hydride

Product 1

HCID 106802064-amino-1-benzylpiperidine-4-carbonitrile

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 3283Diethyl EtherSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of lithium aluminium hydride (1 M in THF, 10.4 ml) in dry diethyl ether (15 ml), cooled to 0° C., under an argon atmosphere is added dropwise 4-amino methyl-1-benzyl-piperidine-4-ylamine (900 mg, 4.18 mmol) in dry diethyl ether (15 ml). The reaction mixture is heated at reflux for 24 h and then cooled to 0° C. Water (0.25 ml) is added followed by a 15% aqueous NaOH (0.25 ml) and then water (0.7 ml). After warming to room temperature MgSO4(150 mg) is added and stirred for 15 minutes. The solids are removed by suction filtration and the filtrate evaporated to give an oil. The solids are extracted with refluxing diethyl ether (80 ml) using a Soxhlet extractor for 14 hours. The diethyl ether is removed in vacuo and the two oils combined and purified by chromatography on silica eluting with 10-25% 2M ammonia in methanol solution in dichloromethane to give 4-Amino-1-benzyl-piperidine-4-carbonitrile; [M+H]+ 220

Workup

  1. temperatureThe reaction mixture is heated
  2. temperatureat reflux for 24 h
  3. additionis added
  4. customThe solids are removed by suction filtration
  5. customthe filtrate evaporated
  6. customto give an oil
  7. extractionThe solids are extracted with refluxing diethyl ether (80 ml)
  8. customfor 14 hours
  9. customThe diethyl ether is removed in vacuo
  10. custompurified by chromatography on silica eluting with 10-25% 2M ammonia in methanol solution in dichloromethane

Sources & evidence

ORD record
ord-a38f3d97f92348d3afa119402e9bd0b3
Source dataset
uspto-grants-2014_04
Patent number
US08697687B2

Reaction notes

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