Water → Zoledronate disodium tetrahydrate

HRID 2246873Notes

Reaction equation

HRID 2246873 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>CO>[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

5

Reactant 3

HCID 962Water2×HCID 14798Sodium HydroxideHCID 68740Zoledronic Acid

Product 1

HCID 23649597Zoledronate disodium tetrahydrateYield 93%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

A 100 ml flask was loaded with Zoledronic acid form I (4.9 g), Sodium hydroxide (1.4 g), Methanol (50 ml) and water (2.5 ml) [=5% v/v water in Methanol]. The reaction mixture was heated to reflux temperature for 21 hours. Then the reaction mixture was cooled to room temperature. Further cooling was performed using an ice-bath. The precipitate was then filtered, washed with absolute Ethanol (2×75 ml) and dried in a vacuum oven at 50° C. for 27.5 hours to give 5.7 g (93%) of Zoledronate disodium crystal form XXVII (LOD by TGA=5.3%). Purity by HPLC 99.9%.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux temperature for 21 hours
  3. temperatureFurther cooling
  4. filtrationThe precipitate was then filtered
  5. washwashed with absolute Ethanol (2×75 ml)
  6. customdried in a vacuum oven at 50° C. for 27.5 hours

Sources & evidence

ORD record
ord-d0d3dc8fa8a24c2aa86845f3c65e50b0
Source dataset
uspto-grants-2010_03
Patent number
US07687636B2

Reaction notes

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