4-Cyano-3-fluorobenzyl bromide → 3-[3-(4-cyano-3-fluoro-benzyl)-3H-imidazol-4-yl]-propionic Acid

Temperature

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

ORD record

ord-62da6c6b6916435fa45d900c7fc79670

Source dataset

uspto-grants-2001_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06316436B1