Triethylamine → tert-Butyl 4-(cyanomethyl)piperidine-1-carboxylate

HRID 1715748Notes

Reaction equation

HRID 1715748 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([CH2:14]O)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:16]([N:18](CC)CC)C.CS(Cl)(=O)=O.[C-]#N.[K+]>C(#N)C.C(O)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([CH2:14][C:16]#[N:18])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 9032Potassium CyanideHCID 31297Methanesulfonyl chlorideHCID 2764081Tert-butyl 4-(hydroxymethyl)piperidine-1-carboxylate

Product 1

HCID 22248390tert-Butyl 4-(cyanomethyl)piperidine-1-carboxylateYield 97.7%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 6342AcetonitrileSolvent

Procedure

To a solution of 4-(hydroxymethyl)piperidine-1-carboxylic acid tert-butyl ester (9.0 g, 42 mmol) in acetonitril (125 mL) was added triethylamine (5.5 g, 54 mmol) followed by dropwise addition of methanesulfonyl chloride (5.7 g, 50 mmol). When addition was complete the mixture was stirred overnight. The mixture was filtered and the solvent was evaporated. The residue was dissolved in ethyl acetate (100 mL) and the organic solution was washed with water (2×10 mL) and brine. The organic phase was dried (MgSO4) and the solvent was evaporated to give a residue that was dissolved in absolute ethanol (250 mL). Potassium cyanide (8.2 g, 125 mmol) was added and the mixture was heated at reflux overnight. The reaction mixture was allowed to cool to ambient temperature, filtered and the solvent was evaporated. The residue was dissolved in diethyl ether (200 mL) and the organic solution was washed with water (2×20 mL) and then dried (MgSO4) in the presence of activated carbon. The mixture was filtered and the solvent was evaporated to give 9.2 g of 4-(cyanomethyl)piperidine-1-carboxylic acid tert-butyl ester. 1H NMR (400 MHz, CDCl3) δ 1.20-1.33 (m, 2H), 1.46 (s, 9H), 1.77-1.88 (m, 3H), 2.32 (d, 2H), 2.66-2.78 (m, 2H), 4.10-4.23 (m, 2H).

Workup

  1. additionWhen addition
  2. filtrationThe mixture was filtered
  3. customthe solvent was evaporated
  4. dissolutionThe residue was dissolved in ethyl acetate (100 mL)
  5. washthe organic solution was washed with water (2×10 mL) and brine
  6. dry with materialThe organic phase was dried (MgSO4)
  7. customthe solvent was evaporated
  8. customto give a residue that
  9. temperaturethe mixture was heated
  10. temperatureat reflux overnight
  11. filtrationfiltered
  12. customthe solvent was evaporated
  13. dissolutionThe residue was dissolved in diethyl ether (200 mL)
  14. washthe organic solution was washed with water (2×20 mL)
  15. dry with materialdried (MgSO4) in the presence of activated carbon
  16. filtrationThe mixture was filtered
  17. customthe solvent was evaporated

Sources & evidence

ORD record
ord-80a5730df8934822a68c57263033cdea
Source dataset
uspto-grants-2010_09
Patent number
US07799924B2

Reaction notes

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