The present invention belongs to the technical field of
organic synthesis, and specifically relates to a method for preparing
azelnidipine with
large particle size. The method comprises the following steps: step 1: adding
azelnidipine crude product to a good
solvent, heating to 30-40°C; step 2: cooling, adding a poor
solvent, and performing the first
crystallization; step 3: heating to 28-33°C, adding a poor
solvent, and performing the second
crystallization; step 4: cooling to 18-23°C, and performing the third
crystallization; step 5: continuing to cool to 8-12°C, and performing the fourth crystallization; step 6: further cooling to 0-5°C, and performing the fifth crystallization, and separating and obtaining
azelnidipine; wherein, in step 1, the good solvent is
dichloromethane; in steps 2 and 3, the poor solvent is n-
heptane. The D90 particle size of the azelnidipine obtained by the present invention is above 110 μm, which can realize the efficient separation of azelnidipine, reduce the production
energy consumption, and the yield and purity of the obtained azelnidipine are high, which is more suitable for industrial production.