Beta-Alanine → Pamidronic Acid

HRID 2420069Notes

Reaction equation

HRID 2420069 reaction equation
P(Cl)(Cl)Cl.[NH2:5][CH2:6][CH2:7][C:8]([OH:10])=O.[P:11]([OH:14])([OH:13])[OH:12].C>O.ClC1C=CC=CC=1>[NH2:5][CH2:6][CH2:7][C:8]([OH:10])([P:11]([OH:14])(=[O:12])[OH:13])[P:11]([OH:14])(=[O:13])[OH:12]

Participants

7

Reactant 4

HCID 239Beta-AlanineHCID 297MethaneHCID 24387Phosphorus trichlorideHCID 107909Phosphorous acid

Product 1

HCID 4674Pamidronic Acid

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 7964ChlorobenzeneSolvent

Procedure

206 gm (1.5 mols) of phosphorus trichloride are slowly dropped while stirring into a mixture heated in a boiling water bath of 89.1 gm (1 mol) of β-alanine, 123 gm (1.5 mols) of phosphorous acid, and 500 ml of chlorobenzene, and heating on the boiling water bath is continued for a further 3 hours. During this time the contents of the flask become solid. After the reaction is finished, 600 ml of water are added and the product is heated for a short time, treated with animal charcoal and filtered while hot. The 3-amino-hydroxypropane-1,1-diphosphonic acid gradually crystallizes out from the aqueous phase in a cooling cabinet. The mother liquor is concentrated and treated with methanol, whereupon still further diphosphonic acid is precipitated. The 3-amino-1-hydroxypropane-1,1-diphosphonic acid is then recrystallized from water.

Workup

  1. temperaturethe product is heated for a short time
  2. filtrationfiltered while hot
  3. customThe 3-amino-hydroxypropane-1,1-diphosphonic acid gradually crystallizes out from the aqueous phase in a cooling cabinet
  4. concentrationThe mother liquor is concentrated
  5. additiontreated with methanol, whereupon still further diphosphonic acid
  6. customis precipitated
  7. customThe 3-amino-1-hydroxypropane-1,1-diphosphonic acid is then recrystallized from water

Sources & evidence

ORD record
ord-08331569982b44c8a9074269b894f48e
Source dataset
uspto-grants-1978_08
Patent number
US04108962

Reaction notes

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