3',4'-Dimethoxycinnamic acid → HCID 2961547, compound

Participants

Reaction Steps

To a solution of 4.35 g (20.95 mmol) of 3-(3,4-dimethoxy-phenyl)-acrylic acid (compound of Example 2; Step 1) in 35 mL of toluene, 3.703 g (22.8 mmol) of 1,1-carbonyldiimidazole was added in portions at 25° C. to 30° C. under inert atmosphere. To the thickened mixture, 15 mL of toluene was added and the resulting mixture was stirred at 25° C. to 30° C. for 60 to 90 min. A solution of N-hydroxy-nicotinimidamide (compound of Example 53; 6 g, 43.7 mmol) in 5 mL of toluene was added to the above reaction mixture at 25° C. to 30° C. The reaction mixture was stirred at 25° C. to 30° C. under nitrogen for 12-14 h, followed by stirring at 100° C. to 105° C. for 6-8 h. After completion of the reaction, the reaction mixture was cooled to 25° C. to 30° C. and quenched with 10 mL of chilled water under stirring at 25° C. to 30° C. The organic layer was separated, and the aqueous layer was washed with 5 mL of toluene. The organic layers were combined and washed with 10 mL of 1N HCl solution, 10 mL of 5% sodium bicarbonate solution and 10 mL of 10% sodium chloride solution. The organic layer was distilled completely to obtain a crude residue, which was purified by column chromatography (silica gel, chloroform-methanol) to yield the title compound.

Provenance & Evidence