Reaction #367520

Reaction equation

1-chloro-2-(ethenyloxy)ethane

1-(4-fluorophenylmethyl)-N-(4-piperidinyl)-1H-benzimidazol-2-amine dihydrobromide

sodium carbonate

potassium iodide

→

N-[1-[2-(ethenyloxy)ethyl]-4-piperidinyl]-1-(4-fluorophenylmethyl)-1H-benzimidazol-2-amine

Yield 32.0%

Solvents

N,N-dimethylformamide

Conditions

Workup

1. 1
   workup.ADDITIONThe reaction mixture was poured onto water
2. 2
   Extractionthe product was extracted with 4-methyl-2-pentanone
3. 3
   OtherThe extract was dried
4. 4
   Filtrationfiltered
5. 5
   Otherevaporated
6. 6
   OtherThe residue was purified by column chromatography over silica gel using
7. 7
   workup.ADDITIONa mixture of trichloromethane and methanol
8. 8
   OtherThe pure fractions were collected
9. 9
   Otherthe eluent was evaporated
10. 10
    OtherThe residue was crystallized from acetonitrile

Procedure

A mixture of 1.6 parts of 1-chloro-2-(ethenyloxy)ethane, 7.3 parts of 1-(4-fluorophenylmethyl)-N-(4-piperidinyl)-1H-benzimidazol-2-amine dihydrobromide, 3.1 parts of sodium carbonate, 0.1 parts of potassium iodide and 135 parts of N,N-dimethylformamide was stirred and heated overnight at 70° C. The reaction mixture was poured onto water and the product was extracted with 4-methyl-2-pentanone. The extract was dried, filtered and evaporated. The residue was purified by column chromatography over silica gel using a mixture of trichloromethane and methanol, saturated with ammonia, (96:4 by volume) as eluent. The pure fractions were collected and the eluent was evaporated. The residue was crystallized from acetonitrile, yielding 1.9 parts (32%) of N-[1-[2-(ethenyloxy)ethyl]-4-piperidinyl]-1-(4-fluorophenylmethyl)-1H-benzimidazol-2-amine; mp. 138.5° C. (compound 1).

Source