4-Cyano-3-fluorobenzyl bromide → Methyl 1-(4-cyano-3-fluorobenzyl)imidazol-5-ylacetate

Participants

Reaction Conditions

Reaction Steps

A solution of methyl 1-(triphenylmethyl)imidazol-4-ylacetate from Step B (0.536 g, 1.40 mmol) and 4-cyano-3-fluoro-benzylbromide from Example 1, Step D (0.300 g, 1.40 mmol) in dry acetonitrile (3 mL) was heated at 50° C. under argon for 2 hours, then the precipitate was collected by filtration. The filtrate was concentrated to a volume of 1 mL and then heated at 50° C. for a further 2 hours. The precipitate formed was collected and combined with the first crop to give a white solid (0.63 g). This solid was dissolved in MeOH (30 mL) and heated to reflux for 2 hours. The MeOH was removed under reduced pressure and the residue was partitioned between sat. aq. 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 under reduced pressure. The residue was purified by flash column chromatography, eluting with 3% MeOH/0.3% NH4OH in CHCl3 to give the titled product as a white solid.

Provenance & Evidence