Dimethylformamide → Zoledronate disodium tetrahydrate

HRID 730606Notes

Reaction equation

HRID 730606 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-844d4c3d4c2c46019b97e812f7349d66
Source dataset
uspto-grants-2009_09
Patent number
US07582768B2

Reaction notes

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