Beta-Alanine → Pamidronic Acid

HRID 412673

Reaction equation

HRID 412673 reaction equation
[P:1]([OH:4])([OH:3])[OH:2].[NH2:5][CH2:6][CH2:7][C:8]([OH:10])=O.N1CCOCC1.P(Cl)(Cl)Cl>>[CH2:7]([C:8]([P:1]([OH:4])([OH:3])=[O:2])([P:1]([OH:4])([OH:3])=[O:2])[OH:10])[CH2:6][NH2:5]

Participants

5

Reactant 4

HCID 239Beta-AlanineHCID 8083MorpholineHCID 24387Phosphorus trichlorideHCID 107909Phosphorous acid

Product 1

HCID 4674Pamidronic Acid

Conditions

Temperature
70 °C

Procedure

The mixture of 5 eq. phosphorous acid and β-alanine is heated to form a melt. Morpholine (1 eq.) is slowly added. The reaction is cooled to about 70° C. and 2 eq. of PCl3 are added. The mixture is heated for about 3.5 hours. Then the reaction is hydrolyzed in aqueous acid at about 75° C. for about 0.5 hours. Crystallization from aqueous acid/IPA, affords pamidronate.

Workup

  1. temperatureis heated
  2. customto form a melt
  3. temperatureThe mixture is heated for about 3.5 hours
  4. customCrystallization from aqueous acid/IPA

Sources & evidence

ORD record
ord-1073b756d7524ebf91ed74ed69b1f293
Source dataset
uspto-grants-2003_05
Patent number
US06562974B2

Linked notes

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