Methanol → Benzimidazole

HRID 1723156Notes

Reaction equation

HRID 1723156 reaction equation
FC1C=CC([C:8]2[N:12](O)[C:11]3[CH:14]=[C:15](C(N4C=CN=C4)C4C=CC=CC=4)[CH:16]=[CH:17][C:10]=3[N:9]=2)=CC=1.[OH-].[Na+].CO>O>[NH:9]1[C:10]2[CH:17]=[CH:16][CH:15]=[CH:14][C:11]=2[N:12]=[CH:8]1

Participants

5

Reactant 3

HCID 887MethanolHCID 14798Sodium HydroxideHCID 14518691HCID 14518691, compound

Product 1

HCID 5798Benzimidazole

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A mixture of 2.7 parts of 2-(4-fluorophenyl)-6-[(1H-imidazol-1-yl)-phenylmethyl]-1H-benzimidazol-1-ol, 7 parts of a sodium hydroxide solution in water 1N and 20 parts of methanol was stirred for 15 minutes at room temperature. After evaporation, the residue was taken up in methylbenzene and the solvent was evaporated (this proces was repeated twice). The residue was dissolved in 22.5 parts of N,N-dimethylformamide and a solution of 0.89 parts of (chloromethyl)benzene in a small amount of N,N-dimethylformamide was added dropwise. Upon complete addition, stirring was continued for 1 hour at room temperature. After standing overnight at room temperature, the solvent was evaporated. Water was added to the residue and the product was extracted with dichloromethane. The extract was dried, filtered and concentrated. The concentrate was purified by column chromatography over silica gel using a mixture of trichloromethane and methanol (95:5 by volume) as eluent. The pure fractions were collected and the eluent was evaporated. The residue was crystallized from 17.5 parts of 2-propanol. The product was filtered off, washed with 2,2'-oxybispropane and 2-propanol and dried, yielding 2.1 parts (63.5%) of 2-(4-fluorophenyl)-6-[(1H-imidazol-1-yl)phenylmethyl]-1-phenylmethoxy)-1H-benzimidazole; mp. 177.6° C. (compound 241).

Workup

  1. customAfter evaporation
  2. customthe solvent was evaporated (this proces
  3. dissolutionThe residue was dissolved in 22.5 parts of N,N-dimethylformamide
  4. additiona solution of 0.89 parts of (chloromethyl)benzene in a small amount of N,N-dimethylformamide was added dropwise
  5. additionUpon complete addition
  6. stirringstirring
  7. waitwas continued for 1 hour at room temperature
  8. waitAfter standing overnight at room temperature
  9. customthe solvent was evaporated
  10. additionWater was added to the residue
  11. extractionthe product was extracted with dichloromethane
  12. customThe extract was dried
  13. filtrationfiltered
  14. concentrationconcentrated
  15. customThe concentrate was purified by column chromatography over silica gel using
  16. additiona mixture of trichloromethane and methanol (95:5 by volume) as eluent
  17. customThe pure fractions were collected
  18. customthe eluent was evaporated
  19. customThe residue was crystallized from 17.5 parts of 2-propanol
  20. filtrationThe product was filtered off
  21. washwashed with 2,2'-oxybispropane and 2-propanol
  22. customdried

Sources & evidence

ORD record
ord-760ef685e9a34aa4883e478a11e53999
Source dataset
uspto-grants-1989_08
Patent number
US04859684

Reaction notes

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