Methanol → Zoledronate disodium tetrahydrate

HRID 733456Notes

Reaction equation

HRID 733456 reaction equation
[OH-:1].[Na+:2].CO.[CH:5]1[N:9]=[CH:8][N:7]([CH2:10][C:11]([P:17]([OH:20])([OH:19])=[O:18])([P:13]([OH:16])([OH:15])=[O:14])[OH:12])[CH:6]=1>O>[CH:5]1[N:9]=[CH:8][N:7]([CH2:10][C:11]([P:13]([O-:16])([OH:15])=[O:14])([P:17]([O-:19])([OH:20])=[O:18])[OH:12])[CH:6]=1.[OH2:1].[OH2:12].[OH2:12].[OH2:12].[Na+:2].[Na+:2]

Participants

5

Reactant 3

HCID 887Methanol2×HCID 14798Sodium HydroxideHCID 68740Zoledronic Acid

Product 1

HCID 23649597Zoledronate disodium tetrahydrate

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Procedure

A solution of sodium hydroxide (1.4 g) in a mixture of water (X % v/v)/Methanol (Y % v/v, 10 volumes per grams of ZLD-Ac form I) (15 ml) was added drop-wise to a suspension of Zoledronic acid form I (5.0 g) in a mixture of water (X % v/v)/Methanol (Y % v/v, 10 volumes per grams of ZLD-Ac) (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. Purity by HPLC 99.95%.

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-73875d8c73e442bc9072cc0aeae80642
Source dataset
uspto-grants-2009_09
Patent number
US07589211B2

Reaction notes

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