반응 #75168

반응 방정식

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

용매

water

4-methyl-2-pentanone

water

반응 조건

후처리

1. 1
   기타The layers are separated
2. 2
   기타the organic phase is dried
3. 3
   여과filtered
4. 4
   기타evaporated
5. 5
   기타The 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
   기타The pure fractions are collected
8. 8
   기타the eluent is evaporated
9. 9
   workup.DISSOLUTIONThe oily residue is dissolved in 2-propanone
10. 10
    workup.STIRRINGthe whole is stirred
11. 11
    온도refluxed for 15 minutes
12. 12
    기타The solvent is evaporated
13. 13
    workup.DISSOLUTIONthe formed hydrochloride salt is dissolved in water
14. 14
    추출The product is extracted with 4-methyl-2-pentanone
15. 15
    기타The extract is dried
16. 16
    여과filtered
17. 17
    기타evaporated
18. 18
    기타The residue is crystallized from methylbenzene
19. 19
    여과The product is filtered off
20. 20
    기타dried

실험 절차

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.

출처