Sodium Hydroxide → Zoledronate disodium tetrahydrate

HRID 733463Notes

Reaction equation

HRID 733463 reaction equation
[OH-:1].[Na+:2].[CH:3]1[N:7]=[CH:6][N:5]([CH2:8][C:9]([P:15]([OH:18])([OH:17])=[O:16])([P:11]([OH:14])([OH:13])=[O:12])[OH:10])[CH:4]=1>O.CC(O)C.CO.C(O)C>[CH:3]1[N:7]=[CH:6][N:5]([CH2:8][C:9]([P:11]([O-:14])([OH:13])=[O:12])([P:15]([O-:17])([OH:18])=[O:16])[OH:10])[CH:4]=1.[OH2:1].[OH2:10].[OH2:10].[OH2:10].[Na+:2].[Na+:2]

Participants

7

Reactant 2

HCID 14798Sodium HydroxideHCID 68740Zoledronic Acid

Product 1

HCID 23649597Zoledronate disodium tetrahydrate

Reagents, catalysts & solvents 4

HCID 702EthanolSolvent2×HCID 887MethanolSolvent2×HCID 962WaterSolvent2×HCID 3776IsopropanolSolvent3×

Procedure

A solution of sodium hydroxide (0.7 g) in a mixture of water (80% v/v)/Ethanol or Methanol or IPA (20% v/v, 10 volumes per grams of ZLD-Ac form XII) (38 ml) was added drop-wise to a suspension of Zoledronic acid form XII (4.98 g) in a mixture of water (80% v/v)/Ethanol or Methanol or 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. 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 VII.

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-8fd9f02a23af40929b25ae4bf7a2b41a
Source dataset
uspto-grants-2009_09
Patent number
US07589211B2

Reaction notes

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