Method for preparing 2-hydroxyl-4-(2, 3-disubstituted benzyloxy)-5-substituted benzaldehyde derivative

A method for preparing 4-(2, 3-disubstituted benzyloxy)-2-hydroxy-5-substituted benzaldehyde derivative (I):

• wherein the method comprises the following steps:
• 1) preparing 3-aryl-2-substituted toluene derivative 2 from 3-iodo-2-substituted toluene derivative 1 and aryl boronic acid 5, or an aryl boronate thereof, as starting materials:
• wherein “a” means that 3-iodo-2-substituted toluene derivative 1 and aryl boronic acid 5, or an aryl boronate thereof, are subjected to a Suzuki-Miyaura coupling reaction to form 3-aryl-2-substituted toluene derivative 2 in the presence of a palladium catalyst and a base;
• 2) preparing benzyl halide derivative 3 from 3-aryl-2-substituted toluene derivative 2 as a starting material:
• wherein “b” means that 3-aryl-2-substituted toluene derivative 2 is reacted with a halogenating agent under radical-initiating condition to prepare a benzyl halide derivative 3;
• 3) preparing 4-(2, 3-disubstituted benzyloxy)-2-hydroxy-5-substituted benzaldehyde derivative (I) from benzyl halide derivative 3 and 2,4-dihydroxy-5-substituted benzaldehyde 6 as starting materials:
• wherein “c” means that benzyl halide derivative 3 is reacted with 2, 4-dihydroxy-5-substituted benzaldehyde 6 in a weak basic condition to selectively prepare a 4-(2, 3-disubstituted benzyloxy)-2-hydroxy-5-substituted benzaldehyde derivative (I);
• wherein:
• R1 is selected from fluorine, chlorine, bromine, methyl, and cyano;
• R2 is selected from
• R3 is selected from hydrogen, methyl, ethyl, fluorine, chlorine, and bromine;
• X selected from bromine, chlorine, and iodine.