Reaktion #75168

Reaktionsgleichung

sodium hydroxide

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

4-(4-fluorophenyl)-4-piperidinol

sodium carbonate

→

1-{3-[4-(4-fluorophenyl)-4-hydroxy-1-piperidinyl]propyl}-1,3-dihydro-2H-benzimidazol-2-one

Lösungsmittel

water

4-methyl-2-pentanone

water

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeThe layers are separated
2. 2
   Sonstigethe organic phase is dried
3. 3
   Filtrationfiltered
4. 4
   Sonstigeevaporated
5. 5
   SonstigeThe residue is purified by column-chromatography over silica gel using
6. 6
   workup.ADDITIONa mixture of trichloromethane and 10% of methanol as eluent
7. 7
   SonstigeThe pure fractions are collected
8. 8
   Sonstigethe eluent is evaporated
9. 9
   workup.DISSOLUTIONThe oily residue is dissolved in 2-propanone
10. 10
    workup.STIRRINGthe whole is stirred
11. 11
    Temperaturrefluxed for 15 minutes
12. 12
    SonstigeThe solvent is evaporated
13. 13
    workup.DISSOLUTIONthe formed hydrochloride salt is dissolved in water
14. 14
    ExtraktionThe product is extracted with 4-methyl-2-pentanone
15. 15
    SonstigeThe extract is dried
16. 16
    Filtrationfiltered
17. 17
    Sonstigeevaporated
18. 18
    SonstigeThe residue is crystallized from methylbenzene
19. 19
    FiltrationThe product is filtered off
20. 20
    Sonstigedried

Vorschrift

A mixture of 5 parts of 1-(3-chloropropyl)-1,3-dihydro-3-(1-methylethenyl)-2H-benzimidazol-2-one, 3.9 parts of 4-(4-fluorophenyl)-4-piperidinol, 5.3 parts of sodium carbonate and 80 parts of 4-methyl-2-pentanone is stirred and refluxed for 48 hours with water-separator. The reaction mixture is cooled to room temperature, water is added and the whole is alkalized with 15 parts of a sodium hydroxide solution 60%. The layers are separated and the organic phase is dried, filtered and evaporated. The residue is purified by column-chromatography over silica gel using a mixture of trichloromethane and 10% of methanol as eluent. The pure fractions are collected and the eluent is evaporated. The oily residue is dissolved in 2-propanone. The solution is acidified with 2-propanol, previously saturated with gaseous hydrogen chloride, and the whole is stirred and refluxed for 15 minutes. The solvent is evaporated and the formed hydrochloride salt is dissolved in water. The free base is liberated in the conventional manner with a diluted sodium hydroxide solution. The product is extracted with 4-methyl-2-pentanone. The extract is dried, filtered and evaporated. The residue is crystallized from methylbenzene. The product is filtered off and dried, yielding 2.5 parts of 1-{3-[4-(4-fluorophenyl)-4-hydroxy-1-piperidinyl]propyl}-1,3-dihydro-2H-benzimidazol-2-one; mp. 135.4° C.

Quelle