Preparation method of (E)-4-(imidazolyl methyl) cinnamate

[0037] Add 305g (4.5mol, 1.5eq) of imidazole, 180g (4.5mol, 1.5eq) of sodium hydroxide, and 1.5L of tetrahydrofuran into a 10L reaction flask, and stir at room temperature for 30min to fully react imidazole and sodium hydroxide. Cool down -5°C to 0°C and continue stirring; dissolve 765g (3.0mol, 1.0eq) of methyl 4-bromomethyl cinnamate in 3.0L tetrahydrofuran, stir to dissolve into a solution, and gradually add it dropwise to In the reaction system, after the addition is complete, keep at -5°C to 0°C to continue the reaction for 2 hours, then stop the reaction; add 3N hydrochloric acid to adjust the pH to 6-7, concentrate the reaction solution under reduced pressure, recover the solvent, pour the residue into a 20L transfer barrel, and continue Add 10 L of water, stir and crystallize, filter, and dry the filter cake at 60°C to constant weight to obtain a white solid weighing 690 g, with a yield of 95.0%. 99.52% purity.

[0039] Add 205g (3.0mol, 1.2eq) of imidazole, 185g (3.3mol, 1.3eq) of potassium hydroxide, and 1.5L of N,N-dimethylformamide into a 5L reaction flask, and stir at room temperature for 30min to make imidazole and potassium hydroxide fully responsive. Cool down to 0°C to 5°C and continue stirring; dissolve 635g (2.5mol, 1.0eq) of methyl 4-bromomethyl cinnamate in 2.0L N,N-dimethylformamide, stir to dissolve into a solution, and drop Drop the liquid funnel into the reaction system step by step. After the addition, keep the 0℃~5℃ to continue the reaction for 2h, stop the reaction; add 3N hydrochloric acid to adjust the pH to 6~7, pour the reaction solution into a 20L transfer bucket, continue to add 10L of water, and stir Crystallize, filter, and dry the filter cake at 60° C. to constant weight to obtain a white solid weighing 550 g with a yield of 91.2%. 98.88% purity.

[0041] Add 340g of imidazole (5.0mol, 2.0eq), 280g of potassium hydroxide (5.0mol, 2.0eq), 1.8L of acetonitrile into a 10L reaction flask, stir and react at room temperature for 1h, the system turns into an orange-red liquid, and control the temperature at 0°C to 5 Continue to stir the reaction for 30 min at ℃; dissolve 670 g (2.5 mol, 1.0 eq) of ethyl 4-bromomethyl cinnamate in 3.0 L of acetonitrile, stir to dissolve, and dissolve ethyl 4-bromomethyl cinnamate in batches The acetonitrile solution was gradually added dropwise into the imidazole / potassium hydroxide reaction system through the dropping funnel. After the addition was complete, the reaction was continued at 0°C to 5°C for 3 hours, and the reaction was monitored by TLC (developing solvent: ethyl acetate / isopropanol / water / ammonia water =7ml / 14ml / 5ml / 0.6ml, UV254nm) to stop the reaction until the raw materials disappear; add acetic acid to adjust the pH to 6-7, concentrate the reaction solution under reduce