Reaction #55041

Reaction equation

hydrochloric acid

N-(4-chlorophenyl)-1-(1-methylethyl)-4-piperidinamine

3,4-dichlorobenzeneacetyl chloride

sodium hydroxide

sodium amide

→

3,4-dichloro-N-(4-chlorophenyl)-N-[1-(1-methylethyl)-4-piperidinyl]benzeneacetamide

Solvents

water

benzene

benzene

benzene

Conditions

Workup

1. 1
   workup.STIRRINGUpon completion, the whole is stirred
2. 2
   Temperaturerefluxed for 16h.45
3. 3
   TemperatureThe mixture is cooled to 25° C.
4. 4
   workup.ADDITIONthere is added
5. 5
   workup.STIRRINGAfter stirring
6. 6
   Temperaturerefluxing for 2 additional hours
7. 7
   Temperaturethe reaction mixture is cooled
8. 8
   Extractionthe free base is extracted with trichloromethane
9. 9
   OtherThe extract is dried
10. 10
    Filtrationfiltered
11. 11
    Otherevaporated
12. 12
    workup.DISSOLUTIONThe residue is dissolved in a mixture of 80 parts of 1,1'-oxybisethane and 120 parts of hexane
13. 13
    TemperatureThe solution is cooled overnight at -10° C.
14. 14
    Filtrationfiltered from some impurities
15. 15
    Otherthe filtrate is evaporated again
16. 16
    workup.DISSOLUTIONThe residue is dissolved in 120 parts of 1,1'-oxybisethane
17. 17
    workup.ADDITIONtreated with activated charcoal
18. 18
    Filtrationfiltered
19. 19
    Otherevaporated
20. 20
    OtherThe latter residue is crystallized from hexane at -10° C.

Procedure

a suspension of 1.25 parts of sodium amide in 56 parts of benzene is stirred under nitrogen atmosphere and warmed to a temperature of 40° C. Then there is added dropwise a solution of 6 parts of N-(4-chlorophenyl)-1-(1-methylethyl)-4-piperidinamine in 56 parts of benzene. Upon completion, the whole is stirred and refluxed for 16h.45. The mixture is cooled to 25° C. and there is added a mixture of 7.8 parts of 3,4-dichlorobenzeneacetyl chloride in 88 parts of benzene. After stirring and refluxing for 2 additional hours, the reaction mixture is cooled and 80 parts of water are added. The whole is acidified with a diluted hydrochloric acid solution. The aqueous acid phase is alkalized with sodium hydroxide solution and the free base is extracted with trichloromethane. The extract is dried, filtered and evaporated. The residue is dissolved in a mixture of 80 parts of 1,1'-oxybisethane and 120 parts of hexane. The solution is cooled overnight at -10° C., filtered from some impurities and the filtrate is evaporated again. The residue is dissolved in 120 parts of 1,1'-oxybisethane, treated with activated charcoal, filtered and evaporated. The latter residue is crystallized from hexane at -10° C., yielding 2.2 parts of 3,4-dichloro-N-(4-chlorophenyl)-N-[1-(1-methylethyl)-4-piperidinyl]benzeneacetamide; mp. 101.7° C.

Source