Isopropanol → Zoledronate disodium tetrahydrate

HRID 730593Notes

Reaction equation

HRID 730593 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 tetrahydrate

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Procedure

A solution of sodium hydroxide (0.7 g) in a mixture of water (X % v/v)/IPA (Y % v/v, 10 volumes per grams of ZLD-Ac form XII) (13-15 ml) was added drop-wise to a suspension of Zoledronic acid (4.98 g) in a mixture of water (X % v/v)/IPA (Y % v/v, 10 volumes per grams of ZLD-Ac form XII) (70-85 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. Further cooling was performed using an ice-bath. The precipitate was then filtered, washed and dried in a vacuum oven at 50° C. for 24 hours to give Zoledronate disodium crystal form V.

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. temperatureFurther cooling
  6. filtrationThe precipitate was then filtered
  7. washwashed
  8. customdried in a vacuum oven at 50° C. for 24 hours

Sources & evidence

ORD record
ord-62ec656fb42f44bdb7cc56842f07a279
Source dataset
uspto-grants-2009_09
Patent number
US07582768B2

Reaction notes

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