Sodium Hydroxide → Ibandronate Sodium Anhydrous

HRID 229908Notes

Reaction equation

HRID 229908 reaction equation
[CH3:1][CH2:2][CH2:3][CH2:4][CH2:5][N:6]([CH2:8][CH2:9][C:10]([P:16]([OH:19])([OH:18])=[O:17])([P:12]([OH:15])([OH:14])=[O:13])[OH:11])[CH3:7].[OH-].[Na+:21]>CO>[CH3:1][CH2:2][CH2:3][CH2:4][CH2:5][N:6]([CH2:8][CH2:9][C:10]([P:16]([O-:19])([OH:18])=[O:17])([P:12]([OH:15])([OH:14])=[O:13])[OH:11])[CH3:7].[Na+:21]

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 60852Ibandronate

Product 1

HCID 23670359Ibandronate Sodium AnhydrousYield 87.9%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A slurry of amorphous ibandronic acid (5 g) in methanol (50 ml) was heated to reflux temperature. Sodium hydroxide (0.63 g, solid) was added, and the reaction mixture was stirred at reflux temperature for an additional 4 hours to obtain a pH of 4.0. Then the reaction mixture was cooled to room temperature. Further cooling was performed using an ice-bath. The white solid was filtered, washed with methanol (2×25 ml), and dried in a vacuum oven at 50° C. for 19 hours to give 4.7 g of ibandronate sodium crystal form Q3.

Workup

  1. temperatureto reflux temperature
  2. temperatureat reflux temperature for an additional 4 hours
  3. customto obtain a pH of 4.0
  4. temperatureFurther cooling
  5. filtrationThe white solid was filtered
  6. washwashed with methanol (2×25 ml)
  7. customdried in a vacuum oven at 50° C. for 19 hours

Sources & evidence

ORD record
ord-4b6ffe43b806497f8975195a50bb2b36
Source dataset
uspto-grants-2009_07
Patent number
US07563918B2

Reaction notes

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