반응 #75192

반응 방정식

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

수율 46.0%

용매

4-methyl-2-pentanone

water

반응 조건

후처리

1. 1
   온도refluxed for 18 hours
2. 2
   온도After cooling
3. 3
   기타the layers are separated
4. 4
   기타The organic phase is dried
5. 5
   여과filtered
6. 6
   기타evaporated
7. 7
   workup.DISSOLUTIONThe residue is dissolved in 40 parts of ethanol
8. 8
   workup.STIRRINGThe whole is stirred for 30 minutes
9. 9
   기타the solvent is evaporated
10. 10
    추출The product is extracted with trichloromethane
11. 11
    기타The extract is dried
12. 12
    여과filtered
13. 13
    기타evaporated
14. 14
    기타The 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
    기타The pure fractions are collected
17. 17
    기타the eluent is evaporated
18. 18
    기타The residue is crystallized from a mixture of N,N-dimethylformamide and water
19. 19
    여과The product is filtered off
20. 20
    기타dried

실험 절차

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.

출처