Ethanol → Zoledronate disodium tetrahydrate

HRID 733458Notes

Reaction equation

HRID 733458 reaction equation
[OH-:1].[Na+:2].C([OH:5])C.CC([OH:9])C.[CH:10]1[N:14]=[CH:13][N:12]([CH2:15][C:16]([P:22]([OH:25])([OH:24])=[O:23])([P:18]([OH:21])([OH:20])=[O:19])[OH:17])[CH:11]=1>O.CO>[CH:10]1[N:14]=[CH:13][N:12]([CH2:15][C:16]([P:18]([O-:21])([OH:20])=[O:19])([P:22]([O-:24])([OH:25])=[O:23])[OH:17])[CH:11]=1.[OH2:5].[OH2:9].[OH2:1].[OH2:5].[Na+:2].[Na+:2]

Participants

7

Reactant 4

HCID 702Ethanol2×HCID 3776Isopropanol2×HCID 14798Sodium HydroxideHCID 68740Zoledronic Acid

Product 1

HCID 23649597Zoledronate disodium tetrahydrate

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent2×

Procedure

A solution of sodium hydroxide (0.7 g) in a mixture of water (60% v/v)/Ethanol or Methanol (40% v/v, 10 volumes per grams of ZLD-Ac form XII) (19 ml) was added drop-wise to a suspension of Zoledronic acid form XII (4.98 g) in a mixture of water (60% v/v)/Ethanol or Methanol (40% v/v, 10 volumes per grams of ZLD-Ac) (106 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 VI.

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-d5003e7270414326936798b485a0488c
Source dataset
uspto-grants-2009_09
Patent number
US07589211B2

Reaction notes

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