Improved synthesis process of antihypertensive efonidipine hydrochloride

Abstract

The invention discloses an improved synthesis process of antihypertensive efonidipine hydrochloride, which comprises the following steps: synthesis of Nbenzyl aniline: adding 37.23 g (0.4 mol) aniline, 10.10 g (0.12 mol) sodium bicarbonate and 100mL of distilled water into a 250mL three-necked bottle, heating the bottle to 90-95 DEG C while stirring, slowly dripping 12.65 g (0.1 mol) benzyl chloride into the three-necked bottle by using a constant-pressure dropping funnel, performing a reaction under TLC (petroleum ether / ethyl acetate = 20 / 1) monitoring; after the reaction is complete after 2hours, stopping the reaction and cooling hte reaction liquid; performing suction filtration, ethyl acetate extraction and water washing for three times, drying the product with anhydrous sodium sulfate and filtering out the drying agent, performing pressure reduced evaporation to remove the solvent, carrying out reduced pressure distillation and collecting the fractions at 147-150 DEG C / 8 mmHg arecollected, thereby obtaining 15.97 g of a yellow liquid at the yield of 87.2%. According to the invention, in the synthesis of 3-oxobutyric acid-2-(N-benzyl-N-phenyl)amino ethyl ester is used for replacing the used 2,2-dimethyl-1,3-dioxa-4,6-cyclohexanedione, so that the reaction cost is reduced, the post-treatment is not needed, the synthesis in the step (5) is directly carried out, and the experimental operation is simplified.

Description

Technical field[0001]The invention relates to the technical field of ifodipine hydrochloride, in particular to an improved synthesis process of antihypertensive ifodipine hydrochloride.Background technique[0002]Ifodipine hydrochloride is used for the treatment of primary, renal hypertension and hypertension combined with type 2 diabetes, the drug belongs to BCS class II drug, that is, it has low solubility and high membrane permeability. Therefore, it is necessary to improve the drug's performance through the corresponding preparation process The dissolution rate or apparent solubility can achieve the purpose of improving the bioavailability.[0003]The current improved synthesis process of ifodipine hydrochloride has high reaction cost and low reaction yield. When people are operating, the process is cumbersome, which increases the reaction cost, and the experimental operation is very complicated, which affects the reaction yield and is inconvenient for people. use.Summary of the inv...

AI Technical Summary

Problems solved by technology

[0005] Aiming at the deficiencies in the prior art, the present invention provides an improved synthesis process of antihypertensive efodipine hydrochloride, which has the advantages of low reaction cost and high reaction yield, and solves the existing improved synthesis process of efodipine hydrochloride, The reaction cost is high and the reaction yield is low. When people operate, the process is cumbersome, which increases the reaction cost. The experimental operation is very complicated, which affects the reaction yield and is inconvenient for people to use.

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