Scheme 2.

Synthesis of the quercetin-3-O-substituted benzoic acid esters and 3-O-substituted quercetin derivatives.

	R1		R1		R1		R2
4a	H	4f	3''-F	4k	4''-F	12a	Me
4b	2''-F	4g	3''-NH2	4l	4''-NH2	12b	i-Pr
4c	2''-NH2	4h	3''-OCH3	4m	4''-OCH3	12c	(CH2)2OH
4d	2''-OCH3	4i	3''-CN	4n	4''-CN	12d	(CH2)3CN
4e	2''-CN	4j	3''-Cl	4o	4''-Cl

Reagents and conditions: (a) K₂CO₃, BnBr, DMF, 60 °C, 3 h, then HCl con., ethanol, 70 °C, 2 h, 85%; (b) R¹-PhCOOH, EDCI, DMAP, DMF, rt, overnight; (c) H₂, Pd/C, 1,4-dioxane/ethanol, rt, 6 h, 40%–79% (two steps); (d) R²Br or R²I, K₂CO₃, DMF, 40 °C, 3 h.