METHOD FOR PREPARING 3-PYRIDYL-1-HYDROXYETHYLIDENE-1,1-BISPHOSPHINIC ACID SODIUM SALT (RIZEDRONATE) IN CRYSTALLINE SEMI-PENTAHYDRATE FORM Russian patent published in 2008 - IPC C07F9/58 

FIELD: chemical technology.

SUBSTANCE: invention relates to a method for synthesis of 3-pyridyl-1-hydroxyethylidene-1,1-bisphosphinic acid sodium salt. Method involves the following steps: (a) 3-pyridyl-1-hydroxyethylidene-1,1-bisphosphinic acid is dissolved in mixture of isopropyl alcohol, water and inorganic sodium base in the amount providing pH 6; (b) this solution is heated to temperature from 50^°C to 60^°C; (c) solution is filtered; (d) pH value of filtered off solution is brought about to 4.7-5 with inorganic acid and temperature is maintained at the level of step (b) to obtain a neutralized solution; (e) solution is cooled to temperature from 20^°C to 40^°C to form seed charge-forming pulp of 3-pyridyl-1-hydroxyethylidene-1,1-bisphosphinic acid salt; (f) isopropyl alcohol and sufficient amount or an inorganic acid are added to this pulp to provide pH value from 4.7 to 5.2 and to form the final pulp of 3-pyridyl-1-hydroxyethylidene-1,1-bisphosphinic acid salt in crystalline semi-pentahydrate form, and (g) 3-pyridyl-1-hydroxethylidene-1,1-bisphosphinic acid semi-pentahydrate salt is separated. Also, invention proposes variants for synthesis of 3-pyridyl-1-hydroxyethylidene-1,1-bisphosphinic acid sodium salt. Invention provides synthesis of rizedronate in crystalline form of semi-pentahydrate that is free from impurity of other hydrate forms.

EFFECT: improved method of synthesis.

27 cl