Sodium hydride → tert-Butyl 4-cyano-4-(2,4-dichlorophenyl)piperidine-1-carboxylate

HRID 1066997Notes

Reaction equation

HRID 1066997 reaction equation
[C:1]([O:5][C:6](=[O:14])[N:7]([CH2:11][CH2:12]Cl)[CH2:8][CH2:9]Cl)([CH3:4])([CH3:3])[CH3:2].[Cl:15][C:16]1[CH:21]=[C:20]([Cl:22])[CH:19]=[CH:18][C:17]=1[CH2:23][C:24]#[N:25].[H-].[Na+]>CN(C=O)C>[C:1]([O:5][C:6]([N:7]1[CH2:11][CH2:12][C:23]([C:24]#[N:25])([C:17]2[CH:18]=[CH:19][C:20]([Cl:22])=[CH:21][C:16]=2[Cl:15])[CH2:9][CH2:8]1)=[O:14])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 805662,4-DichlorophenylacetonitrileHCID 11230235N-BOC-N,N-Bis(2-chloroethyl)amine

Product 1

HCID 49760258tert-Butyl 4-cyano-4-(2,4-dichlorophenyl)piperidine-1-carboxylateYield 45.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To bis(2-chloroethyl)-carbamic acid tert-butyl ester (1.0 g, 3.8 mmol) and 2,4-dichlorophenyl acetonitrile (0.708 g, 3.8 mmol) in DMF (35 ml), NaH (95%) (0.258 g, 9.68 mmol) was added in one batch at 0° C. The solution was stirred for 10 minutes at room temperature. When foaming subsided, the solution was heated at 60° C. for 24 hours. It was then quenched with water at 0° C. and concentrated. The residue was extracted with ethyl acetate (25 mL) and washed three times with water (15 mL). The organic layer was dried over sodium sulfate, filtered and concentrated. Purification by column chromatography (hexane:ethyl acetate 4:1) yielded 0.620 g (45%) of the product as a syrup.

Workup

  1. temperaturethe solution was heated at 60° C. for 24 hours
  2. customIt was then quenched with water at 0° C.
  3. concentrationconcentrated
  4. extractionThe residue was extracted with ethyl acetate (25 mL)
  5. washwashed three times with water (15 mL)
  6. dry with materialThe organic layer was dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customPurification by column chromatography (hexane:ethyl acetate 4:1)

Sources & evidence

ORD record
ord-6fb5428e61214450b5b5ef68a13ac896
Source dataset
uspto-grants-2001_06
Patent number
US06245773B1

Reaction notes

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