4-Quinolinecarboxaldehyde → HCID 86716085, compound

Participants

Reaction Conditions

Reaction Steps

Analogous to the general method described in J. Org. Chem. 2004, 69, 8115 and Chem. Pharm. Bull 1997, 1145. To a 2-necked flask containing 5-bromo-1-methyl-1H-imidazole (2.05 g, 12.7 mmol) was added THF (50 mL) and the solution was cooled to 0° C. To this clear homogeneous solution was added isopropyl magnesium chloride-LiCl complex (1.3 M, 10.5 mL, 13.6 mmol) which initially resulted in a white suspension, but became grayish once the addition of the Grignard reagent was complete. The reaction was stirred in an ice bath for 30 min, then a THF solution (20 mL) of quinoline-4-carbaldehyde (1.00 g, 6.36 mmol) was introduced and the reaction mixture became a greenish-grey color, and was subsequently allowed to warm to room temp. After 2 hours, the reaction mixture became brown in color and still remained heterogeneous. The reaction was quenched after 2 hours with saturated NH4Cl solution and the aqueous portion was extracted with EtOAc (4×75 mL). The combined organics were washed with brine, dried over MgSO4, filtered and concentrated to give an amber oil which solidified to a white solid upon standing. The crude material was triturated with DCM and then MeOH leaving behind the title compound as a white solid. The mother liquors were concentrated and chromatographed on silica gel (30% EtOAc-DCM increasing gradient to 10% MeOH-DCM) to provide more title compound as an off-white solid.

Provenance & Evidence