Isopropanol → Zoledronate disodium tetrahydrate

HRID 733459Notes

Reaction equation

HRID 733459 reaction equation
[OH-:1].[Na+:2].CC([OH:6])C.[CH:7]1[N:11]=[CH:10][N:9]([CH2:12][C:13]([P:19]([OH:22])([OH:21])=[O:20])([P:15]([OH:18])([OH:17])=[O:16])[OH:14])[CH:8]=1>O>[CH:7]1[N:11]=[CH:10][N:9]([CH2:12][C:13]([P:15]([O-:18])([OH:17])=[O:16])([P:19]([O-:21])([OH:22])=[O:20])[OH:14])[CH:8]=1.[OH2:6].[OH2:1].[OH2:6].[OH2:6].[Na+:2].[Na+:2]

Participants

5

Reactant 3

HCID 3776Isopropanol2×HCID 14798Sodium HydroxideHCID 68740Zoledronic Acid

Product 1

HCID 23649597Zoledronate disodium tetrahydrateYield 78%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Procedure

A solution of sodium hydroxide (1.4 g) in a mixture of water (80% v/v)/IPA (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)/IPA (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 16 hours. Then the reaction mixture was cooled to room temperature and the solution was evaporated to dryness. The obtained solid was dried in a vacuum oven at 50° C. for 5 hours to give 5.2 g (78%) of Zoledronate disodium crystal form VI (LOD by TGA=15.4%). 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 16 hours
  5. customthe solution was evaporated to dryness
  6. customThe obtained solid was dried in a vacuum oven at 50° C. for 5 hours

Sources & evidence

ORD record
ord-72b12ff7fa5b4198b3f6dec66ff2bfb2
Source dataset
uspto-grants-2009_09
Patent number
US07589211B2

Reaction notes

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