Reaktion #75192

Reaktionsgleichung

1-(4-chlorobutyl)-1,3-dihydro-3-(1-methylethenyl)-2H-benzimidazol-2-one

5-chloro-1,3-dihydro-1-(4-piperidinyl)-2H-benzimidazol-2-one

sodium carbonate

potassium iodide

→

5-chloro-1-{1-[4-(2,3-dihydro-2-oxo-1H-benzimidazol-1-yl)butyl]-4-piperidinyl}-1,3-dihydro-2H-benzimidazol-2-one hemihydrate

Ausbeute 46.0%

Lösungsmittel

4-methyl-2-pentanone

water

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturrefluxed for 18 hours
2. 2
   TemperaturAfter cooling
3. 3
   Sonstigethe layers are separated
4. 4
   SonstigeThe organic phase is dried
5. 5
   Filtrationfiltered
6. 6
   Sonstigeevaporated
7. 7
   workup.DISSOLUTIONThe residue is dissolved in 40 parts of ethanol
8. 8
   workup.STIRRINGThe whole is stirred for 30 minutes
9. 9
   Sonstigethe solvent is evaporated
10. 10
    ExtraktionThe product is extracted with trichloromethane
11. 11
    SonstigeThe extract is dried
12. 12
    Filtrationfiltered
13. 13
    Sonstigeevaporated
14. 14
    SonstigeThe residue is purified by column-chromatography over silica gel using
15. 15
    workup.ADDITIONa mixture of trichloromethane and methanol (90:10 by volume) as eluent
16. 16
    SonstigeThe pure fractions are collected
17. 17
    Sonstigethe eluent is evaporated
18. 18
    SonstigeThe residue is crystallized from a mixture of N,N-dimethylformamide and water
19. 19
    FiltrationThe product is filtered off
20. 20
    Sonstigedried

Vorschrift

A mixture of 9.25 parts of 1-(4-chlorobutyl)-1,3-dihydro-3-(1-methylethenyl)-2H-benzimidazol-2-one, 7.55 parts of 5-chloro-1,3-dihydro-1-(4-piperidinyl)-2H-benzimidazol-2-one, 10.6 parts of sodium carbonate, 0.1 parts of potassium iodide and 200 parts of 4-methyl-2-pentanone is stirred and refluxed for 18 hours. After cooling, water is added and the layers are separated. The organic phase is dried, filtered and evaporated. The residue is dissolved in 40 parts of ethanol and the solution is acidified with 30 parts of a concentrated hydrochloric acid solution. The whole is stirred for 30 minutes and the solvent is evaporated. The residue is suspended in water and the suspension is alkalized with ammonium hydroxide. The product is extracted with trichloromethane. The extract is dried, filtered and evaporated. The residue is purified by column-chromatography over silica gel using a mixture of trichloromethane and methanol (90:10 by volume) as eluent. The pure fractions are collected and the eluent is evaporated. The residue is crystallized from a mixture of N,N-dimethylformamide and water. The product is filtered off and dried, yielding 6.5 parts (46%) of 5-chloro-1-{1-[4-(2,3-dihydro-2-oxo-1H-benzimidazol-1-yl)butyl]-4-piperidinyl}-1,3-dihydro-2H-benzimidazol-2-one hemihydrate; mp. 258° C.

Quelle