Sodium hydride → tert-Butyl 4-cyano-4-(3-fluorophenyl)piperidine-1-carboxylate

HRID 2380864Notes

Reaction equation

HRID 2380864 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH2:8][C:9]#[N:10])[CH:5]=[CH:6][CH:7]=1.Cl[CH2:12][CH2:13][N:14]([CH2:22][CH2:23]Cl)[C:15](=[O:21])[O:16][C:17]([CH3:20])([CH3:19])[CH3:18].[H-].[Na+]>CS(C)=O.ClCCl>[C:9]([C:8]1([C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[CH:3]=2)[CH2:23][CH2:22][N:14]([C:15]([O:16][C:17]([CH3:19])([CH3:18])[CH3:20])=[O:21])[CH2:13][CH2:12]1)#[N:10]

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 68145Benzeneacetonitrile, 3-fluoro-HCID 11230235N-BOC-N,N-Bis(2-chloroethyl)amine

Product 1

HCID 23601100tert-Butyl 4-cyano-4-(3-fluorophenyl)piperidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
18 °C

Procedure

A mixture of 3-fluorophenylacetonitrile (200 mg, 1.48 mmol) and tert-butyl bis(2-chloroethyl)carbamate (358 mg, 1.48 mmol) was dissolved in 14.8 mL of anhydrous DMSO. The reaction was purged with a stream of nitrogen and cooled to 18° C. To this reaction was added sodium hydride (358 mg, 1.48 mmol), which was then warmed to ambient temperature and stirred for 2 hours. The reaction was warmed to 50° C. and stirred for 17 hours. The mixture was diluted with dichloromethane (40 mL), washed with water (3×40 mL), and partitioned between water and dichloromethane. The organic layer was dried over sodium sulfate, filtered, concentrated, and subjected to silica gel chromatography eluting with 0-20% EtOAc in hexanes. Collection of product containing fractions and removal of solvent yielded tert-butyl 4-cyano-4-(3-fluorophenyl)piperidine-1-carboxylate.

Workup

  1. customThe reaction was purged with a stream of nitrogen
  2. temperaturewas then warmed to ambient temperature
  3. temperatureThe reaction was warmed to 50° C.
  4. stirringstirred for 17 hours
  5. washwashed with water (3×40 mL)
  6. custompartitioned between water and dichloromethane
  7. dry with materialThe organic layer was dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. washeluting with 0-20% EtOAc in hexanes
  11. customCollection of product
  12. additioncontaining
  13. customfractions and removal of solvent

Sources & evidence

ORD record
ord-62b0812c328a411e8c33e5aa334a1048
Source dataset
uspto-grants-2012_09
Patent number
US08258135B2

Reaction notes

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