Sodium Hydroxide → Zoledronate disodium tetrahydrate

HRID 2246864Notes

Reaction equation

HRID 2246864 reaction equation
[CH:1]1[N:5]=[CH:4][N:3]([CH2:6][C:7]([P:13]([OH:16])([OH:15])=[O:14])([P:9]([OH:12])([OH:11])=[O:10])[OH:8])[CH:2]=1.[OH-:17].[Na+:18]>O>[CH:1]1[N:5]=[CH:4][N:3]([CH2:6][C:7]([P:9]([O-:12])([OH:11])=[O:10])([P:13]([O-:15])([OH:16])=[O:14])[OH:8])[CH:2]=1.[OH2:17].[OH2:8].[OH2:8].[OH2:8].[Na+:18].[Na+:18]

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 68740Zoledronic Acid

Product 1

HCID 23649597Zoledronate disodium tetrahydrateYield 23%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
92 °C

Procedure

A 0.5 liter reactor equipped with a mechanical stirrer, a thermometer, a reflux condenser and a dropping funnel, was loaded with Zoledronic acid form I (10.0 g) and water (130 ml). The suspension was heated to reflux temperature (92° C.) to obtain a clear solution. A 40% aqueous solution of Sodium hydroxide (6.9 g) was added drop-wise. The solution was then cooled to 25° C. was stirred at this temperature for about 16 hours. The solution was then concentrated to half of its volume to obtain a precipitate. The white precipitate was filtered and dried in a vacuum oven at 50° C. for 18.5 hours to obtain 2.8 g (23%) of Zoledronate disodium crystal form VII (LOD by TGA=10.2%). Purity by HPLC 100.0%.

Workup

  1. customA 0.5 liter reactor equipped with a mechanical stirrer
  2. temperatureThe suspension was heated
  3. customto obtain a clear solution
  4. temperatureThe solution was then cooled to 25° C.
  5. concentrationThe solution was then concentrated to half of its volume
  6. customto obtain a precipitate
  7. filtrationThe white precipitate was filtered
  8. customdried in a vacuum oven at 50° C. for 18.5 hours

Sources & evidence

ORD record
ord-b320e9cf8f5a46a1a60f243bf529915a
Source dataset
uspto-grants-2010_03
Patent number
US07687636B2

Reaction notes

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