반응 #367533

반응 방정식

2-furanmethanol

formaldehyde

1-[(4-fluorophenyl)-methyl]-N-(4-piperidinyl)-1H-benzimidazol-2-amine dihydrobromide

→

57

(4-fluorophenylmethyl]-1H-benzimidazol-2-amine

5-[[4-[[1-[(4-fluorophenyl)methyl]-1H-benzimdazol-2-yl]amino]-1-piperidinyl]methyl]-2-furanmethanol

수율 44.0%

용매

water

반응 조건

후처리

1. 1
   기타to reach slowly room temperature
2. 2
   workup.STIRRINGstirring
3. 3
   추출extracted with dichloromethane
4. 4
   기타The extract was dried
5. 5
   여과filtered
6. 6
   기타evaporated
7. 7
   기타The residue was purified by column chromatography over silica gel using first trichloromethane
8. 8
   workup.ADDITIONa mixture of trichloromethane and methanol (90:10 by volume) as eluent
9. 9
   기타The pure fractions were collected
10. 10
    기타the eluent was evaporated
11. 11
    기타It was crystallized from a mixture of 2-propanone and 2,2'-oxybispropane

실험 절차

A mixture of 30 parts of 2-furanmethanol, 300 parts of a formaldehyde solution 4% in water and 145 parts of 1-[(4-fluorophenyl)-methyl]-N-(4-piperidinyl)-1H-benzimidazol-2-amine dihydrobromide was stirred at 3° C. The mixture was allowed to reach slowly room temperature and stirring was continued for 3 days at room temperature. The reaction mixture was alkalized and extracted with dichloromethane. The extract was dried, filtered and evaporated. The residue was purified by column chromatography over silica gel using first trichloromethane and then a mixture of trichloromethane and methanol (90:10 by volume) as eluent. The pure fractions were collected and the eluent was evaporated. The residue was converted into the (E)-2-butenedioate salt and the free base was liberated again in the conventional manner. It was crystallized from a mixture of 2-propanone and 2,2'-oxybispropane, yielding 57 parts (44%) of 5-[[4-[[1-[(4-fluorophenyl)methyl]-1H-benzimdazol-2-yl]amino]-1-piperidinyl]methyl]-2-furanmethanol; mp. 148.8° C. (compound 47).

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