Methanol → Zoledronate disodium tetrahydrate

HRID 733472Notes

Reaction equation

HRID 733472 reaction equation
[OH-:1].[Na+:2].CN(C=[O:7])C.[CH:8]1[N:12]=[CH:11][N:10]([CH2:13][C:14]([P:20]([OH:23])([OH:22])=[O:21])([P:16]([OH:19])([OH:18])=[O:17])[OH:15])[CH:9]=1.CO>O>[CH:8]1[N:12]=[CH:11][N:10]([CH2:13][C:14]([P:16]([O-:19])([OH:18])=[O:17])([P:20]([O-:22])([OH:23])=[O:21])[OH:15])[CH:9]=1.[OH2:7].[OH2:1].[OH2:7].[OH2:7].[Na+:2].[Na+:2]

Participants

6

Reactant 4

HCID 887MethanolHCID 6228Dimethylformamide2×HCID 14798Sodium HydroxideHCID 68740Zoledronic Acid

Product 1

HCID 23649597Zoledronate disodium tetrahydrateYield 90%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Procedure

A solution of sodium hydroxide (0.7 g) in a mixture of water (20% v/v)/Methanol (80% v/v, 10 volumes per grams of ZLD-Ac form XII) (10 ml) was added drop-wise to a suspension of Zoledronic acid form XII (4.98 g) in a mixture of water (20% v/v)/Methanol (80% v/v, 10 volumes per grams of ZLD-Ac) (53 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 with Methanol (2×15 ml) and dried in a vacuum oven at 50° C. for 24 hours to give 4.85 g (90%) of Zoledronate disodium crystal form XXVII (LOD by TGA=7.5%).

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 with Methanol (2×15 ml)
  8. customdried in a vacuum oven at 50° C. for 24 hours

Sources & evidence

ORD record
ord-00c1446f0a40455c9b6b29fe8dd9bf3f
Source dataset
uspto-grants-2009_09
Patent number
US07589211B2

Reaction notes

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