Sodium Hydroxide → Ibandronate Sodium Anhydrous

HRID 229918Notes

Reaction equation

HRID 229918 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(O)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 87.9%

Reagents, catalysts & solvents 1

HCID 19096565Water ethanolSolvent2×

Procedure

A solution of sodium hydroxide (0.63 g) in water:ethanol (60:40 v/v, 19 ml) was added dropwise to a solution of amorphous ibandronic acid (5 g) in water:ethanol (60:40 v/v, 106 ml) at reflux temperature. The reaction mixture was heated at reflux temperature for an additional 3.5 hours to obtain a pH of 4.03. Then the reaction mixture was cooled to room temperature. Further cooling was performed using an ice-bath. The precipitate was filtered, washed with ethanol (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 R.

Workup

  1. temperatureat reflux temperature
  2. temperatureThe reaction mixture was heated
  3. temperatureat reflux temperature for an additional 3.5 hours
  4. customto obtain a pH of 4.03
  5. temperatureFurther cooling
  6. filtrationThe precipitate was filtered
  7. washwashed with ethanol (2×25 ml)
  8. customdried in a vacuum oven at 50° C. for 19 hours

Sources & evidence

ORD record
ord-718e6f54357c4bb5bfa0409a6231acb8
Source dataset
uspto-grants-2009_07
Patent number
US07563918B2

Reaction notes

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