Dimethylformamide → Zoledronate disodium tetrahydrate

HRID 2246869Notes

Reaction equation

HRID 2246869 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>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

5

Reactant 3

HCID 6228Dimethylformamide3×HCID 14798Sodium HydroxideHCID 68740Zoledronic Acid

Product 1

HCID 23649597Zoledronate disodium tetrahydrateYield 92%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Procedure

A solution of sodium hydroxide (0.7 g) in a mixture of water (20% v/v)/DMF (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)/DMF (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 DMF (2×10 ml) and dried in a vacuum oven at 50° C. for 24 hours to give 4.8 g (92%) of Zoledronate disodium crystal form XIV (LOD by TGA=1.9%).

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 with DMF (2×10 ml)
  8. customdried in a vacuum oven at 50° C. for 24 hours

Sources & evidence

ORD record
ord-5ec44ff2e90d4a3185231e6011f79c56
Source dataset
uspto-grants-2010_03
Patent number
US07687636B2

Reaction notes

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