تفاعل #75192

معادلة التفاعل

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

المردود 46.0%

المذيبات

4-methyl-2-pentanone

water

ظروف التفاعل

المعالجة

1. 1
   درجة الحرارةrefluxed for 18 hours
2. 2
   درجة الحرارةAfter cooling
3. 3
   أخرىthe layers are separated
4. 4
   أخرىThe organic phase is dried
5. 5
   ترشيحfiltered
6. 6
   أخرىevaporated
7. 7
   workup.DISSOLUTIONThe residue is dissolved in 40 parts of ethanol
8. 8
   workup.STIRRINGThe whole is stirred for 30 minutes
9. 9
   أخرىthe solvent is evaporated
10. 10
    استخلاصThe product is extracted with trichloromethane
11. 11
    أخرىThe extract is dried
12. 12
    ترشيحfiltered
13. 13
    أخرىevaporated
14. 14
    أخرىThe 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
    أخرىThe pure fractions are collected
17. 17
    أخرىthe eluent is evaporated
18. 18
    أخرىThe residue is crystallized from a mixture of N,N-dimethylformamide and water
19. 19
    ترشيحThe product is filtered off
20. 20
    أخرىdried

الإجراء التجريبي

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.

المصدر