Overview[1][2]
4-Bromomethylphenylacetic acid is a common organic synthesis intermediate and is widely used in the synthesis of pesticides and pharmaceutical intermediates.
Preparation method[1-2]
Method 1
Dissolve 50g of compound 1 (4-methylphenylacetic acid) into 200 ml of carbon tetrachloride, heat to reflux, and add NBS (N-bromosuccinimide) (62g) in batches while heating. 0.35mol), continue to maintain the reflux state for 3 hours after the addition, a large amount of solids precipitate out, TLC shows that the raw material reaction is complete, cool the reaction solution to room temperature, pour into 500 ml of ice water while stirring, continue stirring for 20 minutes, and filter , the filter cake was washed three times with water (300 ml each time) to obtain a white solid. The white solid was dried at 50°C for 10 hours to obtain 51g of compound 2 (4-bromomethylphenylacetic acid).
Method 2
Put the raw material p-toluene acetic acid (24 grams) into a 250 ml three-port, add 80 ml of chlorobenzene, 30 g of NBS, and 0.6 g of azobisisobutyronitrile, and heat to 85°C under mechanical stirring. After the reaction is initiated, the temperature will automatically rise to 110°C to control the reaction between 90 and 110°C, and the reaction will be kept in this temperature range for 4 hours. The TLC plate will monitor that the reaction is complete. After cooling, a solid precipitated. After filtration, the filter cake was washed with water and filtered as dry as possible. The resulting white solid weighed 33.0 grams after drying, with a yield of 90% and an HPLC purity of 98.7%. 1HNMR (DMSO-d6, 300MHz) δ: 12.2 (s, 1H), 7.18-7.23 (m, 4H), 4.69 (s, 2H), 3.57 (s, 2H).
This method uses p-methylphenylacetic acid as raw material, high boiling point reagent as solvent, triggers the reaction under light irradiation, and prepares p-bromomethylphenylacetic acid with high yield and high purity efficiently and conveniently. Since the present invention uses a high-boiling point reaction solvent, after the reaction is initiated by light, a large amount of heat generated can be taken away by the high-boiling point solvent through circulation. At the same time, after cooling, the product 4-bromomethylphenylacetic acid is precipitated from the solvent, washed with water, and dried. The obtained HPLC purity is greater than 98.5%, and the yield is as high as 90%.
Main reference materials
[1][China Invention] CN201610356984.6 A preparation method of AR-13324
[2][Chinese invention] CN201710165988.0 A method for preparing p-bromomethylphenylacetic acid
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