Sodium hydride → 3-[2-(4-Piperidyl)ethyl]benzonitrile hydrochloride

HRID 2074296Notes

Reaction equation

HRID 2074296 reaction equation
[H-].[Na+].[Br-].[C:4]([C:6]1[CH:7]=[C:8]([CH:29]=[CH:30][CH:31]=1)[CH2:9][P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)#[N:5].[CH:32]([CH:34]1[CH2:39][CH2:38][N:37](C(OC(C)(C)C)=O)[CH2:36][CH2:35]1)=O.[H][H].[ClH:49].CCOC(C)=O>CCOC(C)=O.[C].[Pd].CN(C=O)C>[ClH:49].[NH:37]1[CH2:38][CH2:39][CH:34]([CH2:32][CH2:9][C:8]2[CH:7]=[C:6]([CH:31]=[CH:30][CH:29]=2)[C:4]#[N:5])[CH2:35][CH2:36]1

Participants

9

Reactant 5

HCID 24758Sodium hydrideHCID 1514430tert-Butyl 4-formylpiperidine-1-carboxylateHCID 2778355(3-Cyanobenzyl)triphenylphosphonium bromideHCID 21866389Hydrogen chloride-ethyl acetateHCID 178418361HCID 178418361, compound

Product 1

HCID 574218243-[2-(4-Piperidyl)ethyl]benzonitrile hydrochloride

Reagents, catalysts & solvents 3

HCID 178418390HCID 178418390, compoundCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent3×

Procedure

Under ice cooling, sodium hydride (60% oil, 141 mg) was added to a DMF (20 ml) solution of (3-cyanobenzyl)(triphenyl)phosphonium bromide (1.6 g) and tert-butyl 4-formyl-1-piperidinecarboxylate (0.75 g), followed by stirring overnight at room temperature. The reaction liquid was diluted with EtOAc, washed with water, and dried over anhydrous magnesium sulfate. The solvent was evaporated, and the resulting residue was purified by silica gel column chromatography (eluent: hexane:EtOAc=6:1 (v/v)) to obtain an oil. 10% Palladium-carbon (100 mg) was added to an EtOAc (30 ml) solution of the resulting oil, followed by stirring in a hydrogen stream atmosphere for 2 hours. The catalyst was removed with Celite, and the solvent was concentrated to obtain an oil. The resulting oil was dissolved in EtOAc (10 ml), and 4 M hydrogen chloride/EtOAc solution (5 ml) was added thereto, then stirred at room temperature for 6 hours, and then concentrated. The resulting solid was washed with ether and dried under reduced pressure to obtain 3-[2-(4-piperidinyl)ethyl]benzonitrile hydrochloride (506 mg).

Workup

  1. customThe reaction liquid
  2. washwashed with water
  3. dry with materialdried over anhydrous magnesium sulfate
  4. customThe solvent was evaporated
  5. customthe resulting residue was purified by silica gel column chromatography (eluent: hexane:EtOAc=6:1 (v/v))
  6. customto obtain an oil
  7. customThe catalyst was removed with Celite
  8. concentrationthe solvent was concentrated
  9. customto obtain an oil
  10. stirringstirred at room temperature for 6 hours
  11. concentrationconcentrated
  12. washThe resulting solid was washed with ether
  13. customdried under reduced pressure

Sources & evidence

ORD record
ord-c48d3155ad3948a793bc0f6c1564f467
Source dataset
uspto-grants-2011_04
Patent number
US07919495B2

Reaction notes

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