Zoledronic acid hydrate synthesis

Yield:165800-06-6 89%

Reaction Conditions:

with water at 70 - 80;Heating / reflux;

Steps:

3

Example 3 - Zoledronic Acid Monohydrate; The raw humid zoledronic acid (equivalent to 90.3 g raw product), obtained according to Example 1, is suspended in water (3050 ml). The suspension is heated at reflux, with agitation. EPO Water is added up to a total volume of 3750 ml, by which a total dissolution is obtained.The heating is then interrupted and the agitation, allowing it to slowly cool down to ambient temperature.Once the inside temperature is around 70 - 80⁰C a frank crystallization starts.Once the ambient temperature is reached, it is cooled down to 2 - 5 ⁰C, maintained at that temperature during 1 'Λ hours, filtered and the precipitate is washed with ice water.It is dried in a stove with air flow at 5°C - 60 ⁰C.169.3 g (89 %) colorless crystals are obtained.The loss through dissection (6.8%) confirms that this is a monohydrate.This substance, by diffraction with X-rays, dust method, presents peaks at the following values of 20 12.1; 12.8; 15.7; 18.9 +/- 0.2, coincident with those described for the form I (US 2005/0054616).Figure I A shows its diffractogram of dust X-rays and figure IV A the lay-out of the atoms in the unitary cell of the crystalline network for this form.

References:

WO2007/16982,2007,A1 Location in patent:Page/Page column 7-8