Sodium Hydroxide → Ibandronate Sodium Anhydrous

HRID 229910Notes

Reaction equation

HRID 229910 reaction equation
[OH-].[Na+:2].[CH3:3][CH2:4][CH2:5][CH2:6][CH2:7][N:8]([CH2:10][CH2:11][C:12]([P:18]([OH:21])([OH:20])=[O:19])([P:14]([OH:17])([OH:16])=[O:15])[OH:13])[CH3:9]>O.C(#N)C>[CH3:3][CH2:4][CH2:5][CH2:6][CH2:7][N:8]([CH2:10][CH2:11][C:12]([P:18]([O-:21])([OH:20])=[O:19])([P:14]([OH:17])([OH:16])=[O:15])[OH:13])[CH3:9].[Na+:2]

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 60852Ibandronate

Product 1

HCID 23670359Ibandronate Sodium AnhydrousYield 73%

Reagents, catalysts & solvents 1

HCID 18373917Acetonitrile--water (1/1)Solvent2×

Procedure

A solution of sodium hydroxide (0.63 g) in water:acetonitrile (40:60 v/v, 12.33 ml) was added dropwise to a solution of amorphous ibandronic acid (5 g) in water:acetonitrile (40:60 v/v, 71 ml) at reflux temperature. The reaction mixture was heated at reflux temperature for an additional 1 hour to obtain a pH of 4.05. Then the reaction mixture was cooled to room temperature. Further cooling was performed using an ice-bath. The precipitate was isolated by vacuum filtration, washed with acetonitrile (2×20 ml), and dried in a vacuum oven at 50° C. for 20 hours to obtain 3.9 g of ibandronate sodium crystal form Q5. Form Q5 can exhibit a weight loss of about 5% to about 11% in TGA.

Workup

  1. temperatureat reflux temperature
  2. temperatureThe reaction mixture was heated
  3. temperatureat reflux temperature for an additional 1 hour
  4. customto obtain a pH of 4.05
  5. temperatureFurther cooling
  6. customThe precipitate was isolated by vacuum filtration
  7. washwashed with acetonitrile (2×20 ml)
  8. customdried in a vacuum oven at 50° C. for 20 hours

Sources & evidence

ORD record
ord-d14d2bb9b63c4ed4970ead936565fac1
Source dataset
uspto-grants-2009_07
Patent number
US07563918B2

Reaction notes

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