Alendronic Acid → Alendronate sodium anhydrous

HRID 2122070Notes

Reaction equation

HRID 2122070 reaction equation
[CH2:1]([CH2:13][NH2:14])[CH2:2][C:3]([P:9]([OH:12])([OH:11])=[O:10])([P:5]([OH:8])([OH:7])=[O:6])[OH:4].O.[Na].[OH-].[Na+:18].C(CN)CC(P(O)(O)=O)(P(O)(O)=O)O>O.C(O)C>[CH2:1]([CH2:13][NH2:14])[CH2:2][C:3]([P:5]([O-:7])([OH:8])=[O:6])([P:9]([OH:12])([OH:11])=[O:10])[OH:4].[Na+:18]

Participants

7

Reactant 4

HCID 2088Alendronic AcidHCID 14798Sodium HydroxideHCID 5360545Sodium2×HCID 15585620Alendronic acid monohydrate2×

Product 1

HCID 16760285Alendronate sodium anhydrous

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent2×

Procedure

In accordance with the aspects of this invention wherein alendronic acid monohydrate is converted to,alendronate sodium, alendronic acid monohydrate as prepared by any of the known methods is added to an alkanol, preferably ethanol, together with a sodium base, preferably sodium hydroxide, and a desired amount of water. The amount of water depends upon the crystal form that is desired. The molar ratio of sodium base to alendronic acid is 1:1. The reaction mixture is boiled under reflux while stirring vigorously for approximately 15 hours, until the pH of the liquid phase remains constant (approx. pH 7). Crystalline alendronate sodium is then isolated, preferably by filtration after cooling to ambient temperature followed by washing with absolute ethanol, washing with absolute ether and drying overnight in a vacuum oven at ambient temperature and at a pressure of 10 mm to 15 mm of mercury.

Workup

  1. customas prepared by any of the known methods
  2. temperatureunder reflux

Sources & evidence

ORD record
ord-2a0370113f454ed7aa1f47e273b38a10
Source dataset
uspto-grants-2004_02
Patent number
US06696601B2

Reaction notes

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