反应详情

温度

55 °C

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.

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