HCID 18433579, compound → HCID 18433508, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of 3-[1-(4-cyano-3-fluorobenzyl)-1H-imidazol-5-yl]-N-methoxy-N-methylpropionamide, as described above in Step A, (505 mg, 1.60 mmol) in dry THF (30 mL) at −78° C., under argon, was added diisobutylaluminum hydride (3.5 mL of a 1.0 M solution in CH2Cl2, 3.5 mmol), dropwise. The reaction mixture was stirred at −78° C. for 2 hours, then quenched with MeOH (1 mL) followed by saturated aqueous sodium potassium tartrate (20 mL). The mixture was allowed to warm to ambient temperature, then extracted with CH2Cl2 (3×30 mL). The combined organic extracts were dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude product was purified by flash column chromatography, eluting with a gradient of CH2Cl2—1% to 6% MeOH—0.1% to 0.6% NH4OH to give a mixture of the desired aldehyde and its methyl hemiacetal. Treatment of this mixture with dilute HCl in MeOH/H2O followed by concentration from toluene afforded the desired aldehyde.

Provenance & Evidence