Ethanol → Zoledronate disodium tetrahydrate

HRID 730605Notes

Reaction equation

HRID 730605 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 tetrahydrateYield 84%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Procedure

A solution of sodium hydroxide (1.4 g) in a mixture of water (5% v/v)/Ethanol (95% v/v, 10 volumes per grams of ZLD-Ac form I) (8 ml) was added drop-wise to a suspension of Zoledronic acid form I (5.0 g) in a mixture of water (5% v/v)/Ethanol (95% v/v, 10 volumes per grams of ZLD-Ac) (45 ml) at reflux temperature. The reaction mixture was heated at reflux temperature for additional 19.5 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 Ethanol (1×10 ml) and dried in a vacuum oven at 50° C. for 20 hours to give 4.9 g (84%) of Zoledronate disodium crystal form XIII (LOD by TGA=3.4%). 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 19.5 hours
  5. temperatureFurther cooling
  6. filtrationThe precipitate was then filtered
  7. washwashed with Ethanol (1×10 ml)
  8. customdried in a vacuum oven at 50° C. for 20 hours

Sources & evidence

ORD record
ord-40f87dd41d7f4ef7aa9168c9e08e3830
Source dataset
uspto-grants-2009_09
Patent number
US07582768B2

Reaction notes

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