The synthetic method of risedronate sodium

Abstract

The invention discloses a synthesis method of risedronate sodium. The synthesis method comprises the following steps of: adding a compound LX-1 and methanol to a flask with a round bottom, cooling down to 15 DEG C below zero, charging dry gaseous hydrochloric acid, reacting at the temperature 10 DEG C below zero, filtering, and distilling to obtain LX-2 imide salt; adding a compound LX-2 and the methanol to a microwave reactor with reaction temperature of 100 DEG C, filtering after finishing the reaction, and decompressing and distilling a solvent to obtain LX-3; adding the compound LX-3 and methyl benzene to a flask with single neck, heating to 90 DEG C, dropwise adding phosphorus trichloride, removing the methyl benzene, adding water for reversely flowing, filtering, adding alcohol to the filtrate, cooling down, crystallizing, filtering, washing and drying to obtain LX-4; and adding the compound LX-4 to the bottle with the signal neck, adding purified water, heating to 60 DEG C, dropwise adding a NaOH solution of 2mol / L, cooling down, crystallizing, filtering and drying to obtain the risedronate sodium. According to the synthesis method disclosed by the invention, the process route is direct, the raw materials are easy to be obtained, the operation is simple, the environment is green and protected, no complex reaction exists, special reagents are not needed, and the yield is higher.

Description

technical field [0001] The invention relates to a synthesis method, in particular to a synthesis method of risedronate sodium. technical background [0002] Risedronate Sodium is a third-generation bisphosphonate drug jointly developed by Procter & Gamble (P&G) and Hoechst Mar ion Roussel. Its tablets were first approved for osteoporosis in October 1999 in Sweden . In April 2000, the US FDA approved this product for the prevention and treatment of postmenopausal osteoporosis and osteoporosis caused by long-term glucocorticoid treatment. [0003] There are two main synthetic methods of 3-pyridineacetic acid hydrochloride, the key intermediate of risedronate sodium: Method 1: It is prepared by esterification, reduction, chlorination, cyanation, and hydrolysis with nicotinic acid as the starting material. The method is harsh and uses expensive reducing agents such as lithium aluminum hydride and highly toxic cyanide. Methods Dinicotinic acid was prepared by esterification, ...

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Problems solved by technology

The method has mild conditions, but the reaction time is long and the processing is cumbersome

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