Ethanol → Zoledronate disodium tetrahydrate

HRID 2115229Notes

Reaction equation

HRID 2115229 reaction equation
[OH-:1].[Na+:2].C([OH:5])C.[CH:6]1[N:10]=[CH:9][N:8]([CH2:11][C:12]([P:18]([OH:21])([OH:20])=[O:19])([P:14]([OH:17])([OH:16])=[O:15])[OH:13])[CH:7]=1>O>[CH:6]1[N:10]=[CH:9][N:8]([CH2:11][C:12]([P:14]([O-:17])([OH:16])=[O:15])([P:18]([O-:20])([OH:21])=[O:19])[OH:13])[CH:7]=1.[OH2:5].[OH2:1].[OH2:5].[OH2:5].[Na+:2].[Na+:2]

Participants

5

Reactant 3

HCID 702Ethanol2×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)/Ethanol (Y % v/v, 10 volumes per grams of ZLD-Ac form I) (10-15 ml) was added drop-wise to a suspension of Zoledronic acid form I (5.0 g) in a mixture of water (X % v/v)/Ethanol (Y % v/v, 10 volumes per grams of ZLD-Ac) (53-85 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 99.9%.

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-ba963f2775dd40b38b3b5b5a0eb26e69
Source dataset
uspto-grants-2008_10
Patent number
US07435827B2

Reaction notes

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