Sodium Hydroxide → Alendronate sodium anhydrous

HRID 2122072Notes

Reaction equation

HRID 2122072 reaction equation
[OH-].[Na+:2].[CH2:3]([CH2:15][NH2:16])[CH2:4][C:5]([P:11]([OH:14])([OH:13])=[O:12])([P:7]([OH:10])([OH:9])=[O:8])[OH:6].O>C(O)C.O>[CH2:3]([CH2:15][NH2:16])[CH2:4][C:5]([P:7]([O-:9])([OH:10])=[O:8])([P:11]([OH:14])([OH:13])=[O:12])[OH:6].[Na+:2]

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 15585620Alendronic acid monohydrate

Product 1

HCID 16760285Alendronate sodium anhydrousYield 96%

Reagents, catalysts & solvents 2

HCID 702EthanolSolvent2×HCID 962WaterSolvent

Procedure

A 250 ml flask was fitted with a mechanical stirrer, a thermometer, and a reflux condenser. The flask was charged with 38.2 ml of a solution of sodium hydroxide in ethanol (0.49 N, 18.7 mmol), 4.8 ml of ethanol, water (0 to 100 mol. eq., according to the crystal form desired), and 5 g (18.7 mmol) of alendronic acid monohydrate. The reaction mixture was boiled with vigorous stirring for about 15 hours until stability of pH of the liquid phase was reached (approx. pH 7). After cooling of the reaction mixture to ambient temperature the precipitate was filtered, washed with absolute ethanol, and dried overnight in a vacuum over (10-15 mm Hg, ambient temperature) to give 96-99% sodium alendronate having the following crystalline forms: crystalline Form B, when 0-4 (preferably 0-2) mol. eq. water were used; crystalline Form F, when 3-5 mol. eq. water were used; crystalline Form E, when 11-13 (preferably 12) mol. eq. water were used; and crystalline Form G, when 15-100 (preferably 20-80) mol. eq. water were used.

Workup

  1. customA 250 ml flask was fitted with a mechanical stirrer
  2. filtrationwas filtered
  3. washwashed with absolute ethanol
  4. customdried overnight in a vacuum over (10-15 mm Hg, ambient temperature)

Sources & evidence

ORD record
ord-8a28c02ad13d4280a144671424e508ef
Source dataset
uspto-grants-2004_02
Patent number
US06696601B2

Reaction notes

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