Ethanol → Zoledronate disodium tetrahydrate

HRID 730603Notes

Reaction equation

HRID 730603 reaction equation
[OH-:1].[Na+:2].C([OH:5])C.[CH:6]1[N:10]=[CH:9][N:8]([CH2:11][C:12]([P:18]([OH:21])([OH:20])=[O:19])([P:14]([OH:17])([OH:16])=[O:15])[OH:13])[CH:7]=1>O>[CH:6]1[N:10]=[CH:9][N:8]([CH2:11][C:12]([P:14]([O-:17])([OH:16])=[O:15])([P:18]([O-:20])([OH:21])=[O:19])[OH:13])[CH:7]=1.[OH2:5].[OH2:1].[OH2:5].[OH2:5].[Na+:2].[Na+:2]

Participants

5

Reactant 3

HCID 702Ethanol2×HCID 14798Sodium HydroxideHCID 68740Zoledronic Acid

Product 1

HCID 23649597Zoledronate disodium tetrahydrateYield 98%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Procedure

A solution of sodium hydroxide (1.4 g) in a mixture of water (80% v/v)/Ethanol (20% v/v, 10 volumes per grams of ZLD-Ac form I) (38 ml) was added drop-wise to a suspension of Zoledronic acid form I (5.0 g) in a mixture of water (80% v/v)/Ethanol (20% v/v, 10 volumes per grams of ZLD-Ac) (212 ml) at reflux temperature. The reaction mixture was heated at reflux temperature for additional 18.5 hours. Then the reaction mixture was cooled to room temperature and the solution was evaporated to dryness to obtain 6.7 g (98%) of Zoledronate disodium crystal form VII (LOD by TGA=16.8%). Purity by HPLC 99.9%.

Workup

  1. additionwas added drop-wise
  2. temperatureat reflux temperature
  3. temperatureThe reaction mixture was heated
  4. temperatureat reflux temperature for additional 18.5 hours
  5. customthe solution was evaporated to dryness

Sources & evidence

ORD record
ord-69bf0cf805224f269647b30003141c7f
Source dataset
uspto-grants-2009_09
Patent number
US07582768B2

Reaction notes

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