Acetonitrile → 5-[(2-Methylbenzofuran-3-yl)carbonyl]-4,5,6,7-tetrahydrobenzimidazole fumarate

HRID 2225620Notes

Reaction equation

HRID 2225620 reaction equation
S(O)(O)(=O)=O.[N:6]1[C:10]2[CH2:11][CH2:12][CH:13]([C:15]([OH:17])=O)[CH2:14][C:9]=2[NH:8][CH:7]=1.S(Cl)(Cl)=O.[C:22]([OH:29])(=[O:28])/[CH:23]=[CH:24]/[C:25]([OH:27])=[O:26].[C:30]([O-:37])(=O)/[CH:31]=[CH:32]/[C:33]([O-])=O.[C:38](#N)[CH3:39]>C(Cl)(Cl)Cl.CO>[C:22]([OH:29])(=[O:28])/[CH:23]=[CH:24]/[C:25]([OH:27])=[O:26].[CH3:24][C:23]1[O:37][C:30]2[CH:31]=[CH:32][CH:33]=[CH:39][C:38]=2[C:22]=1[C:15]([CH:13]1[CH2:12][CH2:11][C:10]2[N:6]=[CH:7][NH:8][C:9]=2[CH2:14]1)=[O:17]

Participants

7

Reactant 5

HCID 6342AcetonitrileHCID 24386Thionyl ChlorideHCID 444972Fumaric AcidHCID 5460307FumarateHCID 148567954,5,6,7-Tetrahydrobenzimidazole-5-carboxylic acid sulfate

Product 1

HCID 189852385-[(2-Methylbenzofuran-3-yl)carbonyl]-4,5,6,7-tetrahydrobenzimidazole fumarate

Reagents, catalysts & solvents 1

HCID 21584188Chloroform methanolSolvent

Conditions

Temperature
55 °C

Procedure

In 40 ml of acetonitrile was suspended 5.00 g of 4,5,6,7-tetrahydrobenzimidazole-5-carboxylic acid sulfate, and 2.75 ml of thionyl chloride was added to the suspension. The suspension was stirred at 55° C. for 1 hour, and the solvent was distilled off under reduced pressure. To the residue was added 20 ml of nitrobenzene and 1.80 ml of 2-methylbenzofurane, and 2.20 ml of tin tetrachloride was then added thereto. After stirring at 85° C. for one night, 40 ml of 1M aqueous hydrochloric acid solution and 40 ml of ethyl ether were added thereto. The organic layer was removed, 40 ml of chloroform was added and then the solution was adjusted to a pH of 9 with 10% aqueous solution of sodium hydroxide. The reaction solution was filtered through celite and then extracted with chloroform containing 10% methanol. The organic layer was collected and the solvent was distilled off. To the free base of objective product obtained by treating the residue with silica gel column chromatography using chloroform/methanol was added calculated amount of fumaric acid to convert it to a fumarate and recrystallized from ethanol to obtain 0.14 g of 5-[(2-methylbenzofuran-3-yl)carbonyl]-4,5,6,7-tetrahydrobenzimidazole fumarate.

Workup

  1. additionwas added to the suspension
  2. distillationthe solvent was distilled off under reduced pressure
  3. additionTo the residue was added 20 ml of nitrobenzene and 1.80 ml of 2-methylbenzofurane, and 2.20 ml of tin tetrachloride
  4. additionwas then added
  5. stirringAfter stirring at 85° C. for one night
  6. addition40 ml of 1M aqueous hydrochloric acid solution and 40 ml of ethyl ether were added
  7. customThe organic layer was removed
  8. addition40 ml of chloroform was added
  9. filtrationThe reaction solution was filtered through celite
  10. extractionextracted with chloroform containing 10% methanol
  11. customThe organic layer was collected
  12. distillationthe solvent was distilled off
  13. customTo the free base of objective product obtained
  14. additionby treating the residue with silica gel column chromatography
  15. additionwas added
  16. customrecrystallized from ethanol

Sources & evidence

ORD record
ord-ee2b411b1f834ce59439af0267812d54
Source dataset
uspto-grants-1994_09
Patent number
US05344927

Reaction notes

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