反应详情

温度

50 °C

A mixture of methyl [1-(triphenylmethyl)-1H-imidazol-4-yl]acetate, as described above in Step B, (536 mg, 1.40 mmol) and 4-cyano-3-fluorobenzyl bromide, as described in Example 1, Step D, (300 mg, 1.40 mmol) in acetonitrile (3 mL) was heated to 50° C. for 2 hours. The mixture was allowed to cool, and the solid collected by filtration. The acetonitrile filtrate was concentrated in vacuo to a volume of approximately 1 mL and then reheated to 50° C. for 2 hours, cooled, and the solid removed by filtration. The two crops of precipitated imidazolium salts were combined in MeOH (30 mL) and the solution was heated to reflux for 2 hours, then concentrated in vacuo. The residue was partitioned between saturated aqueous NaHCO3 (20 mL) and CHCl3 (30 mL). The aqueous layer was extracted further with CHCl3 (2×15 mL). The combined organic extracts were dried over Na2SO4, filtered, and concentrated in vacuo. The crude product was purified by flash column chromatography on silica, eluting with CHCl3—3% MeOH—0.3% NH4OH to CHCl3—5% MeOH—0.5% NH4OH to yield the titled product as a white solid.

1. temperatureto cool
2. filtrationthe solid collected by filtration
3. concentrationThe acetonitrile filtrate was concentrated in vacuo to a volume of approximately 1 mL
4. temperaturecooled
5. customthe solid removed by filtration
6. temperaturethe solution was heated
7. temperatureto reflux for 2 hours
8. concentrationconcentrated in vacuo
9. customThe residue was partitioned between saturated aqueous NaHCO3 (20 mL) and CHCl3 (30 mL)
10. extractionThe aqueous layer was extracted further with CHCl3 (2×15 mL)
11. dry with materialThe combined organic extracts were dried over Na2SO4
12. filtrationfiltered
13. concentrationconcentrated in vacuo
14. customThe crude product was purified by flash column chromatography on silica
15. washeluting with CHCl3—3% MeOH—0.3% NH4OH to CHCl3—5% MeOH—0.5% NH4OH