Step 1: To the reaction flask, add, in order, 160mL of water, 80mL of methanol, 10g of tert-butyl carbamate (85.36mmol), 30.4g of sodium p-toluenesulfinate (170.72mmol), 12.8g of
4-formylphenylboronic acid (85.36 mmol) and 6.5 mL of formic acid were reacted at room temperature for 36 h. The crude product was obtained by filtration, washed with water, washed with methyl tert-butyl ether and dried to obtain a white solid. Then the white solid as well as 600mL THF was added into the reaction flask, stirring was turned on to add 99.5g of potassium carbonate (720mmol), heated to 60C for 15h, after cooling, filtered through diatomaceous earth, concentrated and evaporated the solvent to obtain 15.14g of imine intermediate, yield 71.2%;
Step 2: 15.14g of imine intermediate (60.78 mmol) was dissolved in 150 mL of methanol, 4.6 g of NaBH4 (121.56 mmol) was added in batches, the reaction was carried out at room temperature overnight, and the reduced intermediate was concentrated under reduced pressure. The reduced intermediate was adjusted to pH=5-6 with 1.0M aqueous citric acid, extracted with ethyl acetate, and the organic phase was washed with water and dried to obtain 4-(N-Boc-aminomethyl)phenylboronic acid.
Step 3: 4-(N-Boc-aminomethyl)phenylboronic acid was added to the reaction flask, followed by adding 100mL 3.0M HCl/ethyl acetate solution (), stirring at room temperature for 2h, and filtration to obtain 10.18g of 4-aminomethylphenylboronic acid hydrochloride, yield 89.4%.
