反应详情

温度

60 °C

1-Trityl-imidazole-4-propionic acid methyl ester (2.15 g, 5.42 mmol) and 4-bromomethyl-2-fluoro-benzonitrile, as described above in Step D, (1.16 g, 5.42 mmol) were dissolved in EtOAc (20 mL) and heated at 60° C. for 3 h. The precipitated solid was filtered off, and the filtrate was concentrated to 10 mL then heating at 60° C. was continued overnight. The precipitate was collected and combined with the first solid and heated at reflux in CH3OH (20 mL) for 5 h. The reaction mixture was concentrated to dryness and triturated with hexane to remove triphenylmethane. The residue was dissolved in THF (10 mL)-H2O (5 mL), treated with 1 N NaOH (5 mL) and stirred at ambient temperature for 16 h. The reaction mixture was neutralized with 1N HCl (5 mL), concentrated to remove the THF, then lyophilized to give the title compound.

1. filtrationThe precipitated solid was filtered off
2. concentrationthe filtrate was concentrated to 10 mL
3. temperaturethen heating at 60° C.
4. customThe precipitate was collected
5. temperatureheated
6. temperatureat reflux in CH3OH (20 mL) for 5 h
7. concentrationThe reaction mixture was concentrated to dryness
8. customtriturated with hexane
9. customto remove triphenylmethane
10. dissolutionThe residue was dissolved in THF (10 mL)-H2O (5 mL)
11. additiontreated with 1 N NaOH (5 mL)
12. concentrationconcentrated
13. customto remove the THF