Alendronic Acid → Alendronate sodium anhydrous

HRID 651842ノート

反応式

HRID 651842 の反応式
[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]>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]

参加物

5

反応物 2

HCID 2088Alendronic AcidHCID 14798Sodium Hydroxide

生成物 1

HCID 16760285Alendronate sodium anhydrous収率 96%

試薬・触媒・溶媒 2

HCID 702Ethanol溶媒2 回HCID 962Water溶媒

実験手順

A 250 ml flask was fitted with a mechanical stirrer, a thermometer, and a reflux condenser. The flask was charged with 41.1 ml of a solution of sodium hydroxide in ethanol (0.49N, 20.1 mmol), 8.9 ml of ethanol, water (0 to 40 mol. eq., according to the crystal form desired), and 5g (20.1 mmol) of anhydrous alendronic acid. The reaction mixture was boiled with vigorous stirring for about 15 hours until the of pH of the liquid phase remained constant (approx. pH 7). After cooling of the reaction mixture to ambient temperature, the solid material was filtered, washed with absolute ethanol, and dried overnight in a vacuum oven (10-15 mmHg, ambient temperature) to give 96-99% sodium alendronate having the following crystal forms: crystal Form D, when 0-4 (preferably 0-2) mol. eq. water were used; crystal Form F, when 5-8 (preferably 6-7) mol. eq. water were used; crystal Form E, when 9-15 (preferably 12) mol. eq. water were used; and crystal Form G, when 15-40 (preferably 25-35) mol. eq. water were used. The monosodium salt was confirmed by atomic absorption and by measuring the pH of a 0.5% aqueous solution of the salt (approx. pH 4.4).

後処理

  1. customA 250 ml flask was fitted with a mechanical stirrer
  2. filtrationthe solid material was filtered
  3. washwashed with absolute ethanol
  4. customdried overnight in a vacuum oven (10-15 mmHg, ambient temperature)

出典と根拠

ORDレコード
ord-1de7bbe1afb94b68ad101d23994afd28
出典データセット
uspto-grants-2001_08
特許番号
US06281381B1

反応ノート

読み込み中…