Lithium amide → 4-(4-Fluoro-2-methylphenyl)-1-(4-methylphenylsulfonyl)-4-piperidinecarbonitrile

HRID 1164357Notes

Reaction equation

HRID 1164357 reaction equation
Cl[CH2:2][CH2:3][N:4]([CH2:15][CH2:16]Cl)[S:5]([C:8]1[CH:13]=[CH:12][C:11]([CH3:14])=[CH:10][CH:9]=1)(=[O:7])=[O:6].[F:18][C:19]1[CH:24]=[CH:23][C:22]([CH2:25][C:26]#[N:27])=[C:21]([CH3:28])[CH:20]=1.[NH2-].[Li+]>CC1C=CC=CC=1>[F:18][C:19]1[CH:24]=[CH:23][C:22]([C:25]2([C:26]#[N:27])[CH2:16][CH2:15][N:4]([S:5]([C:8]3[CH:13]=[CH:12][C:11]([CH3:14])=[CH:10][CH:9]=3)(=[O:7])=[O:6])[CH2:3][CH2:2]2)=[C:21]([CH3:28])[CH:20]=1

Participants

5

Reactant 3

HCID 24532Lithium amideHCID 96039N,N-bis(2-chloroethyl)-p-toluenesulphonamideHCID 38654692-(4-Fluoro-2-methylphenyl)acetonitrile

Product 1

HCID 205118204-(4-Fluoro-2-methylphenyl)-1-(4-methylphenylsulfonyl)-4-piperidinecarbonitrileYield 72.6%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Procedure

A solution of 29.6 parts of N,N-bis(2-chloroethyl)-4-methylbenzenesulfonamide and 14.9 parts of 4-fluoro-2-methylbenzeneacetonitrile in 90 parts of methylbenzene is added dropwise to a solution of 5.6 parts of lithium amide in 270 parts of methylbenzene at about 90° C. Upon completion, the whole is heated to reflux and stirred overnight at reflux temperature. The reaction mixture is cooled, poured onto water and the layers are separated. The organic phase is dried, filtered and evaporated. The residue is crystallized from 2-propanol, yielding 27 parts (72.6%) of 4-(4-fluoro-2-methylphenyl)-1-(4-methylphenylsulfonyl)-4-piperidinecarbonitrile.

Workup

  1. temperatureUpon completion, the whole is heated
  2. temperatureto reflux
  3. temperatureat reflux temperature
  4. temperatureThe reaction mixture is cooled
  5. additionpoured onto water
  6. customthe layers are separated
  7. customThe organic phase is dried
  8. filtrationfiltered
  9. customevaporated
  10. customThe residue is crystallized from 2-propanol

Sources & evidence

ORD record
ord-0d4b8d3cefb5432fa8e36670d0c73f4f
Source dataset
uspto-grants-1983_01
Patent number
US04369184

Reaction notes

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