Alendronic Acid → Alendronate sodium anhydrous

HRID 651842노트

반응식

HRID 651842 반응식
[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]

참가 물질

5

반응물 2

HCID 2088Alendronic AcidHCID 14798Sodium Hydroxide

생성물 1

HCID 16760285Alendronate sodium anhydrous수율 96%

시약·촉매·용매 2

HCID 702Ethanol용매2회HCID 962Water용매

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-1de7bbe1afb94b68ad101d23994afd28
출처 데이터셋
uspto-grants-2001_08
특허 번호
US06281381B1

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