Sodium hydride → Tert-butyl 4-(2-chlorophenyl)-4-cyanopiperidine-1-carboxylate

HRID 238289

Reaction equation

HRID 238289 reaction equation
[H-].[Na+].[Cl:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[CH2:10][C:11]#[N:12].[C:13]([O:17][C:18](=[O:26])[N:19]([CH2:23][CH2:24]Cl)[CH2:20][CH2:21]Cl)([CH3:16])([CH3:15])[CH3:14]>CN(C=O)C>[C:13]([O:17][C:18]([N:19]1[CH2:23][CH2:24][C:10]([C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[Cl:3])([C:11]#[N:12])[CH2:21][CH2:20]1)=[O:26])([CH3:16])([CH3:15])[CH3:14]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 76112(o-Chlorophenyl)acetonitrileHCID 11230235N-BOC-N,N-Bis(2-chloroethyl)amine

Product 1

HCID 21712251Tert-butyl 4-(2-chlorophenyl)-4-cyanopiperidine-1-carboxylateYield 30.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Conditions

Temperature
75 °C

Procedure

Sodium hydride (60% dispersion in mineral oil, 1.28 g, 45 mmol) was suspended in DMF (20 mL) and cooled in an ice bath under a nitrogen atmosphere. (2-Chloro-phenyl)-acetonitrile (1.77 g, 11.7 mmol) in DMF (5 mL) was added slowly, and the mixture stirred for 2 hours. Bis-(2-chloro-ethyl)-carbamic acid tert-butyl ester (3.3 g, 11.1 mmol) in DMF (5 mL) was then added and the mixture heated to 75° C. for 6 hours. The solvent was removed by evaporation under vacuum and the residue dissolved in ethyl acetate (50 mL), washed with water, then brine, dried over magnesium sulphate, filtered and the solvent removed by evaporation under vacuum. The residue was purified by silica chromatography eluting with a mixture of ethyl acetate and hexane. The fractions containing the desired products were combined and the solvent removed by evaporation to give the title compound as an orange gum (1.1 g). LCMS m/z 321.0 [M+H]+. R.T.=4.76 min (Analytical Method 4).

Workup

  1. temperaturecooled in an ice bath under a nitrogen atmosphere
  2. customThe solvent was removed by evaporation under vacuum
  3. dissolutionthe residue dissolved in ethyl acetate (50 mL)
  4. washwashed with water
  5. dry with materialbrine, dried over magnesium sulphate
  6. filtrationfiltered
  7. customthe solvent removed by evaporation under vacuum
  8. customThe residue was purified by silica chromatography
  9. washeluting with a mixture of ethyl acetate and hexane
  10. additionThe fractions containing the desired products
  11. customthe solvent removed by evaporation

Sources & evidence

ORD record
ord-6dfa5d3e38844f079e39111db87f1805
Source dataset
uspto-grants-2014_02
Patent number
US08642621B2

Linked notes

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